Hypoxia-Driven Responses in Chronic Kidney Disease
Abstract
:1. Chronic Kidney Disease
2. Hypoxia in the Kidney
2.1. Factors Leading to Hypoxia
2.2. The Hypoxia-Inducible Factor System
2.3. Effects of Hypoxia
2.3.1. Inflammation
2.3.2. Oxidative Stress
2.3.3. Metabolic Reprogramming
2.3.4. Fibrosis
2.4. Influence of Renal Hypoxia in AKI to CKD Progression
3. Hypoxia as a Therapeutic Target in CKD
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
Treatment | Mecanism of Action | Effects | Experimental Model | Reference |
---|---|---|---|---|
CoCl2 | Transcriptional HIF-1α upregulator |
| Subtotal nephrectomy in rats | [210,211] |
| Hypertensive type 2 diabetic rats (SHR/NDmcr-cp) | [158] | ||
| Streptozotocin-induced diabetic nephropathy rats | [156] | ||
| Uninephrectomized Thy1 nephritis rats | [157] | ||
DMOG | Prolyl hydroxylase inhibitor |
| DOCA-salt hypertensive rats | [155] |
| Dahl salt-sensitive rats | [212] | ||
Deferoxamine | Iron chelator, Transcriptional HIF-1α upregulator |
| Unilateral ureteral obstruction | [213] |
Enarodustat | Prolyl hydroxylase inhibitor |
| BTBR ob/ob mice | [166] |
| Subtotal nephrectomy in rats | [167] | ||
Roxadustat | Prolyl hydroxylase inhibitor |
| Adenine-induced nephropathy | [169] |
YC-1 | HIF-1β inhibitor |
| Type 1 diabetic mouse model OVE26 | [214] |
Zinc | Blocks nuclear translocation of HIF-1β |
| Streptozotocin-induced diabetic nephropathy rats | [215] |
References
- Djudjaj, S.; Boor, P. Cellular and molecular mechanisms of kidney fibrosis. Mol. Asp. Med. 2019, 65, 16–36. [Google Scholar] [CrossRef] [PubMed]
- Kazancioglu, R. Risk factors for chronic kidney disease: An update. Kidney Int. Suppl. 2013, 3, 368–371. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- He, L.; Wei, Q.; Liu, J.; Yi, M.; Liu, Y.; Liu, H.; Sun, L.; Peng, Y.; Liu, F.; Venkatachalam, M.A.; et al. AKI on CKD: Heightened injury, suppressed repair, and the underlying mechanisms. Kidney Int. 2017, 92, 1071–1083. [Google Scholar] [CrossRef] [PubMed]
- Cheung, M.D.; Erman, E.N.; Moore, K.H.; Lever, J.M.; Li, Z.; LaFontaine, J.R.; Ghajar-Rahimi, G.; Liu, S.; Yang, Z.; Karim, R.; et al. Resident macrophage subpopulations occupy distinct microenvironments in the kidney. JCI Insight 2022, 7, e161078. [Google Scholar] [CrossRef] [PubMed]
- Lin, N.; Simon, M.C. Hypoxia-inducible factors: Key regulators of myeloid cells during inflammation. J. Clin. Investig. 2016, 126, 3661–3671. [Google Scholar] [CrossRef]
- AIRG-E, EKPF, ALCER, FRIAT, REDINREN, RICORS2040, SENEFRO; SET, ONT. CKD: The burden of disease invisible to research funders. Nefrol. Engl. Ed. 2022, 42, 65–84. [Google Scholar] [CrossRef]
- GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2020, 395, 709–733. [Google Scholar] [CrossRef] [Green Version]
- Chao, C.T.; Chiang, C.K. Uremic toxins, oxidative stress, and renal fibrosis: An interwined complex. J. Ren. Nutr. 2015, 25, 155–159. [Google Scholar] [CrossRef]
- Humphreys, B.D. Mechanisms of Renal Fibrosis. Annu. Rev. Physiol. 2018, 80, 309–326. [Google Scholar] [CrossRef]
- Yu, S.M.; Bonventre, J.V. Acute kidney injury and maladaptive tubular repair leading to renal fibrosis. Curr. Opin. Nephrol. Hypertens. 2020, 29, 310–318. [Google Scholar] [CrossRef]
- Huebener, P.; Schwabe, R.F. Regulation of wound healing and organ fibrosis by toll-like receptors. Biochim. Biophys. Acta 2013, 1832, 1005–1017. [Google Scholar] [CrossRef] [Green Version]
- Duffield, J.S. Cellular and molecular mechanisms in kidney fibrosis. J. Clin. Investig. 2014, 124, 2299–2306. [Google Scholar] [CrossRef] [Green Version]
- Brezis, M.; Heyman, S.N.; Epstein, F.H. Determinants of intrarenal oxygenation. II. Hemodynamic effects. Am. J. Physiol. 1994, 267, F1063–F1068. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Edwards, A. Oxygen transport across vasa recta in the renal medulla. Am. J. Physiol. Heart Circ. Physiol. 2002, 283, H1042–H1055. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thaysen, J.H.; Lassen, N.A.; Munck, O. Sodium transport and oxygen consumption in the mammalian kidney. Nature 1961, 190, 919–921. [Google Scholar] [CrossRef]
- Maxwell, P.H.; Osmond, M.K.; Pugh, C.W.; Heryet, A.; Nicholls, L.G.; Tan, C.C.; Doe, B.G.; Ferguson, D.J.; Johnson, M.H.; Ratcliffe, P.J. Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int. 1993, 44, 1149–1162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hamza, E.; Vallejo-Mudarra, M.; Ouled-Haddou, H.; Garcia-Caballero, C.; Guerrero-Hue, M.; Santier, L.; Rayego-Mateos, S.; Larabi, I.A.; Alvarez, J.C.; Garcon, L.; et al. Indoxyl sulfate impairs erythropoiesis at BFU-E stage in chronic kidney disease. Cell Signal. 2023, 104, 110583. [Google Scholar] [CrossRef] [PubMed]
- Hirakawa, Y.; Tanaka, T.; Nangaku, M. Renal Hypoxia in CKD; Pathophysiology and Detecting Methods. Front. Physiol. 2017, 8, 99. [Google Scholar] [CrossRef] [Green Version]
- Kanbay, A.; Buyukoglan, H.; Ozdogan, N.; Kaya, E.; Oymak, F.S.; Gulmez, I.; Demir, R.; Kokturk, O.; Covic, A. Obstructive sleep apnea syndrome is related to the progression of chronic kidney disease. Int. Urol. Nephrol. 2012, 44, 535–539. [Google Scholar] [CrossRef] [PubMed]
- Welch, W.J. Intrarenal oxygen and hypertension. Clin. Exp. Pharmacol. Physiol. 2006, 33, 1002–1005. [Google Scholar] [CrossRef]
- Iseki, K.; Kohagura, K. Anemia as a risk factor for chronic kidney disease. Kidney Int. Suppl. 2007, 72, S4–S9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yacoub, R.; Habib, H.; Lahdo, A.; Al Ali, R.; Varjabedian, L.; Atalla, G.; Kassis Akl, N.; Aldakheel, S.; Alahdab, S.; Albitar, S. Association between smoking and chronic kidney disease: A case control study. BMC Public Health 2010, 10, 731. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zager, R.A.; Johnson, A.; Anderson, K.; Wright, S. Cholesterol ester accumulation: An immediate consequence of acute in vivo ischemic renal injury. Kidney Int. 2001, 59, 1750–1761. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Norman, J.T.; Clark, I.M.; Garcia, P.L. Hypoxia promotes fibrogenesis in human renal fibroblasts. Kidney Int 2000, 58, 2351–2366. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Falanga, V.; Zhou, L.; Yufit, T. Low oxygen tension stimulates collagen synthesis and COL1A1 transcription through the action of TGF-beta1. J. Cell Physiol. 2002, 191, 42–50. [Google Scholar] [CrossRef]
- Albina, J.E.; Henry, W.L., Jr.; Mastrofrancesco, B.; Martin, B.A.; Reichner, J.S. Macrophage activation by culture in an anoxic environment. J. Immunol. 1995, 155, 4391–4396. [Google Scholar] [CrossRef]
- Luscinskas, F.W.; Ma, S.; Nusrat, A.; Parkos, C.A.; Shaw, S.K. Leukocyte transendothelial migration: A junctional affair. Semin. Immunol. 2002, 14, 105–113. [Google Scholar] [CrossRef]
- Khan, S.; Cleveland, R.P.; Koch, C.J.; Schelling, J.R. Hypoxia induces renal tubular epithelial cell apoptosis in chronic renal disease. Lab. Investig. 1999, 79, 1089–1099. [Google Scholar]
- Mimura, I.; Nangaku, M. The suffocating kidney: Tubulointerstitial hypoxia in end-stage renal disease. Nat. Rev. Nephrol. 2010, 6, 667–678. [Google Scholar] [CrossRef]
- Semenza, G.L. Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu. Rev. Pathol. 2014, 9, 47–71. [Google Scholar] [CrossRef]
- Haase, V.H. Hypoxia-inducible factors in the kidney. Am. J. Physiol. Ren. Physiol. 2006, 291, F271–F281. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nangaku, M.; Eckardt, K.U. Hypoxia and the HIF system in kidney disease. J. Mol. Med. 2007, 85, 1325–1330. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Conde, E.; Alegre, L.; Blanco-Sanchez, I.; Saenz-Morales, D.; Aguado-Fraile, E.; Ponte, B.; Ramos, E.; Saiz, A.; Jimenez, C.; Ordonez, A.; et al. Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival. PLoS ONE 2012, 7, e33258. [Google Scholar] [CrossRef]
- Kojima, I.; Tanaka, T.; Inagi, R.; Kato, H.; Yamashita, T.; Sakiyama, A.; Ohneda, O.; Takeda, N.; Sata, M.; Miyata, T.; et al. Protective role of hypoxia-inducible factor-2alpha against ischemic damage and oxidative stress in the kidney. J. Am. Soc. Nephrol. 2007, 18, 1218–1226. [Google Scholar] [CrossRef] [Green Version]
- Fahling, M.; Mathia, S.; Paliege, A.; Koesters, R.; Mrowka, R.; Peters, H.; Persson, P.B.; Neumayer, H.H.; Bachmann, S.; Rosenberger, C. Tubular von Hippel-Lindau knockout protects against rhabdomyolysis-induced AKI. J. Am. Soc. Nephrol. 2013, 24, 1806–1819. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schofield, C.J.; Ratcliffe, P.J. Oxygen sensing by HIF hydroxylases. Nat. Rev. Mol. Cell Biol. 2004, 5, 343–354. [Google Scholar] [CrossRef] [PubMed]
- Gunter, J.; Ruiz-Serrano, A.; Pickel, C.; Wenger, R.H.; Scholz, C.C. The functional interplay between the HIF pathway and the ubiquitin system—More than a one-way road. Exp. Cell Res. 2017, 356, 152–159. [Google Scholar] [CrossRef] [Green Version]
- Frost, J.; Frost, M.; Batie, M.; Jiang, H.; Rocha, S. Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia. Cancers 2021, 13, 350. [Google Scholar] [CrossRef]
- Laukka, T.; Mariani, C.J.; Ihantola, T.; Cao, J.Z.; Hokkanen, J.; Kaelin, W.G., Jr.; Godley, L.A.; Koivunen, P. Fumarate and Succinate Regulate Expression of Hypoxia-inducible Genes via TET Enzymes. J. Biol. Chem. 2016, 291, 4256–4265. [Google Scholar] [CrossRef] [Green Version]
- Berchner-Pfannschmidt, U.; Tug, S.; Kirsch, M.; Fandrey, J. Oxygen-sensing under the influence of nitric oxide. Cell Signal. 2010, 22, 349–356. [Google Scholar] [CrossRef]
- Liu, Y.V.; Baek, J.H.; Zhang, H.; Diez, R.; Cole, R.N.; Semenza, G.L. RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha. Mol. Cell 2007, 25, 207–217. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Richard, D.E.; Berra, E.; Gothie, E.; Roux, D.; Pouyssegur, J. p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1. J. Biol. Chem. 1999, 274, 32631–32637. [Google Scholar] [CrossRef] [Green Version]
- Geng, H.; Liu, Q.; Xue, C.; David, L.L.; Beer, T.M.; Thomas, G.V.; Dai, M.S.; Qian, D.Z. HIF1alpha protein stability is increased by acetylation at lysine 709. J. Biol. Chem. 2012, 287, 35496–35505. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yasinska, I.M.; Sumbayev, V.V. S-nitrosation of Cys-800 of HIF-1alpha protein activates its interaction with p300 and stimulates its transcriptional activity. FEBS Lett. 2003, 549, 105–109. [Google Scholar] [CrossRef] [Green Version]
- Berta, M.A.; Mazure, N.; Hattab, M.; Pouyssegur, J.; Brahimi-Horn, M.C. SUMOylation of hypoxia-inducible factor-1alpha reduces its transcriptional activity. Biochem. Biophys. Res. Commun. 2007, 360, 646–652. [Google Scholar] [CrossRef] [PubMed]
- Rius, J.; Guma, M.; Schachtrup, C.; Akassoglou, K.; Zinkernagel, A.S.; Nizet, V.; Johnson, R.S.; Haddad, G.G.; Karin, M. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 2008, 453, 807–811. [Google Scholar] [CrossRef] [Green Version]
- Hudson, C.C.; Liu, M.; Chiang, G.G.; Otterness, D.M.; Loomis, D.C.; Kaper, F.; Giaccia, A.J.; Abraham, R.T. Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol. Cell. Biol. 2002, 22, 7004–7014. [Google Scholar] [CrossRef] [Green Version]
- Yan, S.F.; Zou, Y.S.; Mendelsohn, M.; Gao, Y.; Naka, Y.; Du Yan, S.; Pinsky, D.; Stern, D. Nuclear factor interleukin 6 motifs mediate tissue-specific gene transcription in hypoxia. J. Biol. Chem. 1997, 272, 4287–4294. [Google Scholar] [CrossRef] [Green Version]
- Cummins, E.P.; Berra, E.; Comerford, K.M.; Ginouves, A.; Fitzgerald, K.T.; Seeballuck, F.; Godson, C.; Nielsen, J.E.; Moynagh, P.; Pouyssegur, J.; et al. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proc. Natl. Acad. Sci. USA 2006, 103, 18154–18159. [Google Scholar] [CrossRef]
- Batie, M.; Frost, J.; Frost, M.; Wilson, J.W.; Schofield, P.; Rocha, S. Hypoxia induces rapid changes to histone methylation and reprograms chromatin. Science 2019, 363, 1222–1226. [Google Scholar] [CrossRef]
- Shu, S.; Wang, Y.; Zheng, M.; Liu, Z.; Cai, J.; Tang, C.; Dong, Z. Hypoxia and Hypoxia-Inducible Factors in Kidney Injury and Repair. Cells 2019, 8, 207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tanaka, T.; Yamaguchi, J.; Higashijima, Y.; Nangaku, M. Indoxyl sulfate signals for rapid mRNA stabilization of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) and suppresses the expression of hypoxia-inducible genes in experimental CKD and uremia. FASEB J. 2013, 27, 4059–4075. [Google Scholar] [CrossRef]
- Eltzschig, H.K.; Carmeliet, P. Hypoxia and inflammation. N. Engl. J. Med. 2011, 364, 656–665. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sureshbabu, A.; Muhsin, S.A.; Choi, M.E. TGF-beta signaling in the kidney: Profibrotic and protective effects. Am. J. Physiol. Ren. Physiol. 2016, 310, F596–F606. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ludes, P.O.; de Roquetaillade, C.; Chousterman, B.G.; Pottecher, J.; Mebazaa, A. Role of Damage-Associated Molecular Patterns in Septic Acute Kidney Injury, From Injury to Recovery. Front. Immunol. 2021, 12, 606622. [Google Scholar] [CrossRef]
- Santana, A.C.; Degaspari, S.; Catanozi, S.; Delle, H.; de Sa Lima, L.; Silva, C.; Blanco, P.; Solez, K.; Scavone, C.; Noronha, I.L. Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice. Nephrol. Dial. Transplant. 2013, 28, 1140–1149. [Google Scholar] [CrossRef]
- Chen, J.; Tang, T.T.; Cao, J.Y.; Li, Z.L.; Zhong, X.; Wen, Y.; Shen, A.R.; Liu, B.C.; Lv, L.L. KIM-1 augments hypoxia-induced tubulointerstitial inflammation through uptake of small extracellular vesicles by tubular epithelial cells. Mol. Ther. 2022, 31, 1437–1450. [Google Scholar] [CrossRef]
- Chung, S.; Overstreet, J.M.; Li, Y.; Wang, Y.; Niu, A.; Wang, S.; Fan, X.; Sasaki, K.; Jin, G.N.; Khodo, S.N.; et al. TGF-beta promotes fibrosis after severe acute kidney injury by enhancing renal macrophage infiltration. JCI Insight 2018, 3, e123563. [Google Scholar] [CrossRef]
- Lech, M.; Grobmayr, R.; Ryu, M.; Lorenz, G.; Hartter, I.; Mulay, S.R.; Susanti, H.E.; Kobayashi, K.S.; Flavell, R.A.; Anders, H.J. Macrophage phenotype controls long-term AKI outcomes--kidney regeneration versus atrophy. J. Am. Soc. Nephrol. 2014, 25, 292–304. [Google Scholar] [CrossRef] [Green Version]
- Yamaguchi, J.; Tanaka, T.; Eto, N.; Nangaku, M. Inflammation and hypoxia linked to renal injury by CCAAT/enhancer-binding protein delta. Kidney Int. 2015, 88, 262–275. [Google Scholar] [CrossRef] [Green Version]
- Takeda, N.; O’Dea, E.L.; Doedens, A.; Kim, J.W.; Weidemann, A.; Stockmann, C.; Asagiri, M.; Simon, M.C.; Hoffmann, A.; Johnson, R.S. Differential activation and antagonistic function of HIF-alpha isoforms in macrophages are essential for NO homeostasis. Genes Dev. 2010, 24, 491–501. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kobayashi, H.; Gilbert, V.; Liu, Q.; Kapitsinou, P.P.; Unger, T.L.; Rha, J.; Rivella, S.; Schlondorff, D.; Haase, V.H. Myeloid cell-derived hypoxia-inducible factor attenuates inflammation in unilateral ureteral obstruction-induced kidney injury. J. Immunol. 2012, 188, 5106–5115. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tateishi, Y.; Osada-Oka, M.; Tanaka, M.; Shiota, M.; Izumi, Y.; Ishimura, E.; Motoyama, K.; Inaba, M.; Miura, K. Myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive nephropathy. J. Pharmacol. Sci. 2015, 127, 181–189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Awad, A.S.; Rouse, M.; Huang, L.; Vergis, A.L.; Reutershan, J.; Cathro, H.P.; Linden, J.; Okusa, M.D. Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury. Kidney Int. 2009, 75, 689–698. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yago, T.; Petrich, B.G.; Zhang, N.; Liu, Z.; Shao, B.; Ginsberg, M.H.; McEver, R.P. Blocking neutrophil integrin activation prevents ischemia-reperfusion injury. J. Exp. Med. 2015, 212, 1267–1281. [Google Scholar] [CrossRef] [PubMed]
- Peyssonnaux, C.; Datta, V.; Cramer, T.; Doedens, A.; Theodorakis, E.A.; Gallo, R.L.; Hurtado-Ziola, N.; Nizet, V.; Johnson, R.S. HIF-1alpha expression regulates the bactericidal capacity of phagocytes. J. Clin. Investig. 2005, 115, 1806–1815. [Google Scholar] [CrossRef] [Green Version]
- Walmsley, S.R.; Print, C.; Farahi, N.; Peyssonnaux, C.; Johnson, R.S.; Cramer, T.; Sobolewski, A.; Condliffe, A.M.; Cowburn, A.S.; Johnson, N.; et al. Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J. Exp. Med. 2005, 201, 105–115. [Google Scholar] [CrossRef] [Green Version]
- Campbell, E.L.; Bruyninckx, W.J.; Kelly, C.J.; Glover, L.E.; McNamee, E.N.; Bowers, B.E.; Bayless, A.J.; Scully, M.; Saeedi, B.J.; Golden-Mason, L.; et al. Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation. Immunity 2014, 40, 66–77. [Google Scholar] [CrossRef] [Green Version]
- Kapitsinou, P.P.; Sano, H.; Michael, M.; Kobayashi, H.; Davidoff, O.; Bian, A.; Yao, B.; Zhang, M.Z.; Harris, R.C.; Duffy, K.J.; et al. Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury. J. Clin. Investig. 2014, 124, 2396–2409. [Google Scholar] [CrossRef] [Green Version]
- Doedens, A.L.; Phan, A.T.; Stradner, M.H.; Fujimoto, J.K.; Nguyen, J.V.; Yang, E.; Johnson, R.S.; Goldrath, A.W. Hypoxia-inducible factors enhance the effector responses of CD8(+) T cells to persistent antigen. Nat. Immunol. 2013, 14, 1173–1182. [Google Scholar] [CrossRef] [Green Version]
- Moldogazieva, N.T.; Mokhosoev, I.M.; Feldman, N.B.; Lutsenko, S.V. ROS and RNS signalling: Adaptive redox switches through oxidative/nitrosative protein modifications. Free Radic. Res. 2018, 52, 507–543. [Google Scholar] [CrossRef]
- Laurindo, F.R.; Araujo, T.L.; Abrahao, T.B. Nox NADPH oxidases and the endoplasmic reticulum. Antioxid. Redox Signal. 2014, 20, 2755–2775. [Google Scholar] [CrossRef] [Green Version]
- Espinosa-Diez, C.; Miguel, V.; Mennerich, D.; Kietzmann, T.; Sanchez-Perez, P.; Cadenas, S.; Lamas, S. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol. 2015, 6, 183–197. [Google Scholar] [CrossRef] [Green Version]
- Nguyen, T.; Nioi, P.; Pickett, C.B. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J. Biol. Chem. 2009, 284, 13291–13295. [Google Scholar] [CrossRef] [Green Version]
- Oberg, B.P.; McMenamin, E.; Lucas, F.L.; McMonagle, E.; Morrow, J.; Ikizler, T.A.; Himmelfarb, J. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004, 65, 1009–1016. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ho, H.J.; Shirakawa, H. Oxidative Stress and Mitochondrial Dysfunction in Chronic Kidney Disease. Cells 2022, 12, 88. [Google Scholar] [CrossRef] [PubMed]
- Oliveira, F.; Assreuy, J.; Sordi, R. The role of nitric oxide in sepsis-associated kidney injury. Biosci. Rep. 2022, 42, BSR20220093. [Google Scholar] [CrossRef] [PubMed]
- Mapuskar, K.A.; Wen, H.; Holanda, D.G.; Rastogi, P.; Steinbach, E.; Han, R.; Coleman, M.C.; Attanasio, M.; Riley, D.P.; Spitz, D.R.; et al. Persistent increase in mitochondrial superoxide mediates cisplatin-induced chronic kidney disease. Redox Biol. 2019, 20, 98–106. [Google Scholar] [CrossRef]
- Briston, T.; Roberts, M.; Lewis, S.; Powney, B.; Staddon, J.M.; Szabadkai, G.; Duchen, M.R. Mitochondrial permeability transition pore: Sensitivity to opening and mechanistic dependence on substrate availability. Sci. Rep. 2017, 7, 10492. [Google Scholar] [CrossRef] [Green Version]
- Abais, J.M.; Zhang, C.; Xia, M.; Liu, Q.; Gehr, T.W.; Boini, K.M.; Li, P.L. NADPH oxidase-mediated triggering of inflammasome activation in mouse podocytes and glomeruli during hyperhomocysteinemia. Antioxid. Redox Signal. 2013, 18, 1537–1548. [Google Scholar] [CrossRef] [Green Version]
- Nezu, M.; Souma, T.; Yu, L.; Suzuki, T.; Saigusa, D.; Ito, S.; Suzuki, N.; Yamamoto, M. Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression. Kidney Int. 2017, 91, 387–401. [Google Scholar] [CrossRef]
- Wever, R.; Boer, P.; Hijmering, M.; Stroes, E.; Verhaar, M.; Kastelein, J.; Versluis, K.; Lagerwerf, F.; van Rijn, H.; Koomans, H.; et al. Nitric oxide production is reduced in patients with chronic renal failure. Arter. Thromb. Vasc. Biol. 1999, 19, 1168–1172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Godin, N.; Liu, F.; Lau, G.J.; Brezniceanu, M.L.; Chenier, I.; Filep, J.G.; Ingelfinger, J.R.; Zhang, S.L.; Chan, J.S. Catalase overexpression prevents hypertension and tubular apoptosis in angiotensinogen transgenic mice. Kidney Int. 2010, 77, 1086–1097. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Carlstrom, M. Nitric oxide signalling in kidney regulation and cardiometabolic health. Nat. Rev. Nephrol. 2021, 17, 575–590. [Google Scholar] [CrossRef] [PubMed]
- Tumur, Z.; Niwa, T. Indoxyl sulfate inhibits nitric oxide production and cell viability by inducing oxidative stress in vascular endothelial cells. Am. J. Nephrol. 2009, 29, 551–557. [Google Scholar] [CrossRef]
- Li, L.; Kang, H.; Zhang, Q.; D’Agati, V.D.; Al-Awqati, Q.; Lin, F. FoxO3 activation in hypoxic tubules prevents chronic kidney disease. J. Clin. Investig. 2019, 129, 2374–2389. [Google Scholar] [CrossRef] [Green Version]
- Bartoszewska, S.; Collawn, J.F. Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia. Cell. Mol. Biol. Lett. 2020, 25, 18. [Google Scholar] [CrossRef] [Green Version]
- Bhargava, P.; Schnellmann, R.G. Mitochondrial energetics in the kidney. Nat. Rev. Nephrol. 2017, 13, 629–646. [Google Scholar] [CrossRef]
- Hansen, J.; Sealfon, R.; Menon, R.; Eadon, M.T.; Lake, B.B.; Steck, B.; Anjani, K.; Parikh, S.; Sigdel, T.K.; Zhang, G.; et al. A reference tissue atlas for the human kidney. Sci. Adv. 2022, 8, eabn4965. [Google Scholar] [CrossRef]
- Scholz, H.; Boivin, F.J.; Schmidt-Ott, K.M.; Bachmann, S.; Eckardt, K.U.; Scholl, U.I.; Persson, P.B. Kidney physiology and susceptibility to acute kidney injury: Implications for renoprotection. Nat. Rev. Nephrol. 2021, 17, 335–349. [Google Scholar] [CrossRef]
- Li, H.; Dixon, E.E.; Wu, H.; Humphreys, B.D. Comprehensive single-cell transcriptional profiling defines shared and unique epithelial injury responses during kidney fibrosis. Cell Metab. 2022, 34, 1977–1998. [Google Scholar] [CrossRef] [PubMed]
- Lan, R.; Geng, H.; Singha, P.K.; Saikumar, P.; Bottinger, E.P.; Weinberg, J.M.; Venkatachalam, M.A. Mitochondrial Pathology and Glycolytic Shift during Proximal Tubule Atrophy after Ischemic AKI. J. Am. Soc. Nephrol. 2016, 27, 3356–3367. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.W.; Tchernyshyov, I.; Semenza, G.L.; Dang, C.V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006, 3, 177–185. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Faivre, A.; Verissimo, T.; Auwerx, H.; Legouis, D.; de Seigneux, S. Tubular Cell Glucose Metabolism Shift During Acute and Chronic Injuries. Front. Med. 2021, 8, 742072. [Google Scholar] [CrossRef]
- Smith, J.A.; Stallons, L.J.; Schnellmann, R.G. Renal cortical hexokinase and pentose phosphate pathway activation through the EGFR/Akt signaling pathway in endotoxin-induced acute kidney injury. Am. J. Physiol. Ren. Physiol. 2014, 307, F435–F444. [Google Scholar] [CrossRef] [Green Version]
- Zhou, H.L.; Zhang, R.; Anand, P.; Stomberski, C.T.; Qian, Z.; Hausladen, A.; Wang, L.; Rhee, E.P.; Parikh, S.M.; Karumanchi, S.A.; et al. Metabolic reprogramming by the S-nitroso-CoA reductase system protects against kidney injury. Nature 2019, 565, 96–100. [Google Scholar] [CrossRef]
- Kang, H.M.; Ahn, S.H.; Choi, P.; Ko, Y.A.; Han, S.H.; Chinga, F.; Park, A.S.; Tao, J.; Sharma, K.; Pullman, J.; et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat. Med. 2015, 21, 37–46. [Google Scholar] [CrossRef]
- Henderson, N.C.; Rieder, F.; Wynn, T.A. Fibrosis: From mechanisms to medicines. Nature 2020, 587, 555–566. [Google Scholar] [CrossRef]
- Kottmann, R.M.; Kulkarni, A.A.; Smolnycki, K.A.; Lyda, E.; Dahanayake, T.; Salibi, R.; Honnons, S.; Jones, C.; Isern, N.G.; Hu, J.Z.; et al. Lactic Acid Is Elevated in Idiopathic Pulmonary Fibrosis and Induces Myofibroblast Differentiation via pH-Dependent Activation of Transforming Growth Factor-β. Am. J. Respir. Crit. Care Med. 2012, 186, 740–751. [Google Scholar] [CrossRef] [Green Version]
- Li, L.; Galichon, P.; Xiao, X.; Figueroa-Ramirez, A.C.; Tamayo, D.; Lee, J.J.; Kalocsay, M.; Gonzalez-Sanchez, D.; Chancay, M.S.; McCracken, K.W.; et al. Orphan nuclear receptor COUP-TFII enhances myofibroblast glycolysis leading to kidney fibrosis. EMBO Rep. 2021, 22, e51169. [Google Scholar] [CrossRef]
- Wei, Q.; Su, J.; Dong, G.; Zhang, M.; Huo, Y.; Dong, Z. Glycolysis inhibitors suppress renal interstitial fibrosis via divergent effects on fibroblasts and tubular cells. Am. J. Physiol. Ren. Physiol. 2019, 316, F1162–F1172. [Google Scholar] [CrossRef] [PubMed]
- Ding, H.; Jiang, L.; Xu, J.; Bai, F.; Zhou, Y.; Yuan, Q.; Luo, J.; Zen, K.; Yang, J. Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis. Am. J. Physiol. Ren. Physiol. 2017, 313, F561–F575. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, H.; Zhu, J.; Chang, L.; Liang, C.; Li, X.; Wang, W. 3-Bromopyruvate decreased kidney fibrosis and fibroblast activation by suppressing aerobic glycolysis in unilateral ureteral obstruction mice model. Life Sci. 2021, 272, 119206. [Google Scholar] [CrossRef]
- Chini, C.C.S.; Zeidler, J.D.; Kashyap, S.; Warner, G.; Chini, E.N. Evolving concepts in NAD(+) metabolism. Cell Metab. 2021, 33, 1076–1087. [Google Scholar] [CrossRef] [PubMed]
- Covarrubias, A.J.; Perrone, R.; Grozio, A.; Verdin, E. NAD(+) metabolism and its roles in cellular processes during ageing. Nat. Rev. Mol. Cell Biol. 2021, 22, 119–141. [Google Scholar] [CrossRef]
- Ralto, K.M.; Rhee, E.P.; Parikh, S.M. NAD(+) homeostasis in renal health and disease. Nat. Rev. Nephrol. 2020, 16, 99–111. [Google Scholar] [CrossRef]
- Pellicciari, R.; Liscio, P.; Giacche, N.; De Franco, F.; Carotti, A.; Robertson, J.; Cialabrini, L.; Katsyuba, E.; Raffaelli, N.; Auwerx, J. alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide (NAD(+)) Biosynthesis. J. Med. Chem. 2018, 61, 745–759. [Google Scholar] [CrossRef]
- Katsyuba, E.; Mottis, A.; Zietak, M.; De Franco, F.; van der Velpen, V.; Gariani, K.; Ryu, D.; Cialabrini, L.; Matilainen, O.; Liscio, P.; et al. De novo NAD(+) synthesis enhances mitochondrial function and improves health. Nature 2018, 563, 354–359. [Google Scholar] [CrossRef]
- Guan, Y.; Wang, S.R.; Huang, X.Z.; Xie, Q.H.; Xu, Y.Y.; Shang, D.; Hao, C.M. Nicotinamide Mononucleotide, an NAD(+) Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1-Dependent Manner. J. Am. Soc. Nephrol. 2017, 28, 2337–2352. [Google Scholar] [CrossRef] [Green Version]
- Zheng, M.; Cai, J.; Liu, Z.; Shu, S.; Wang, Y.; Tang, C.; Dong, Z. Nicotinamide reduces renal interstitial fibrosis by suppressing tubular injury and inflammation. J. Cell. Mol. Med. 2019, 23, 3995–4004. [Google Scholar] [CrossRef] [Green Version]
- Legouis, D.; Faivre, A.; Cippa, P.E.; de Seigneux, S. Renal gluconeogenesis: An underestimated role of the kidney in systemic glucose metabolism. Nephrol. Dial. Transplant. 2022, 37, 1417–1425. [Google Scholar] [CrossRef]
- Legouis, D.; Ricksten, S.E.; Faivre, A.; Verissimo, T.; Gariani, K.; Verney, C.; Galichon, P.; Berchtold, L.; Feraille, E.; Fernandez, M.; et al. Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality. Nat. Metab. 2020, 2, 732–743. [Google Scholar] [CrossRef]
- Brooks, C.; Wei, Q.; Cho, S.G.; Dong, Z. Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models. J. Clin. Investig. 2009, 119, 1275–1285. [Google Scholar] [CrossRef]
- Xiao, X.; Hu, Y.; Quiros, P.M.; Wei, Q.; Lopez-Otin, C.; Dong, Z. OMA1 mediates OPA1 proteolysis and mitochondrial fragmentation in experimental models of ischemic kidney injury. Am. J. Physiol. Ren. Physiol. 2014, 306, F1318–F1326. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zuo, Z.; Jing, K.; Wu, H.; Wang, S.; Ye, L.; Li, Z.; Yang, C.; Pan, Q.; Liu, W.J.; Liu, H.F. Mechanisms and Functions of Mitophagy and Potential Roles in Renal Disease. Front. Physiol. 2020, 11, 935. [Google Scholar] [CrossRef] [PubMed]
- Cheng, S.C.; Quintin, J.; Cramer, R.A.; Shepardson, K.M.; Saeed, S.; Kumar, V.; Giamarellos-Bourboulis, E.J.; Martens, J.H.; Rao, N.A.; Aghajanirefah, A.; et al. mTOR- and HIF-1alpha-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 2014, 345, 1250684. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bao, H.; Zhang, Q.; Liu, X.; Song, Y.; Li, X.; Wang, Z.; Li, C.; Peng, A.; Gong, R. Lithium targeting of AMPK protects against cisplatin-induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells. FASEB J. 2019, 33, 14370–14381. [Google Scholar] [CrossRef] [Green Version]
- Jin, K.; Ma, Y.; Manrique-Caballero, C.L.; Li, H.; Emlet, D.R.; Li, S.; Baty, C.J.; Wen, X.; Kim-Campbell, N.; Frank, A.; et al. Activation of AMP-activated protein kinase during sepsis/inflammation improves survival by preserving cellular metabolic fitness. FASEB J. 2020, 34, 7036–7057. [Google Scholar] [CrossRef] [Green Version]
- Wculek, S.K.; Dunphy, G.; Heras-Murillo, I.; Mastrangelo, A.; Sancho, D. Metabolism of tissue macrophages in homeostasis and pathology. Cell. Mol. Immunol. 2022, 19, 384–408. [Google Scholar] [CrossRef]
- Higgins, D.F.; Kimura, K.; Bernhardt, W.M.; Shrimanker, N.; Akai, Y.; Hohenstein, B.; Saito, Y.; Johnson, R.S.; Kretzler, M.; Cohen, C.D.; et al. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J. Clin. Investig. 2007, 117, 3810–3820. [Google Scholar] [CrossRef] [Green Version]
- Wang, S.; Zeng, H.; Chen, S.T.; Zhou, L.; Xie, X.J.; He, X.; Tao, Y.K.; Tuo, Q.H.; Deng, C.; Liao, D.F.; et al. Ablation of endothelial prolyl hydroxylase domain protein-2 promotes renal vascular remodelling and fibrosis in mice. J. Cell. Mol. Med. 2017, 21, 1967–1978. [Google Scholar] [CrossRef] [PubMed]
- Eng, E.; Holgren, C.; Hubchak, S.; Naaz, P.; Schnaper, H.W. Hypoxia regulates PDGF-B interactions between glomerular capillary endothelial and mesangial cells. Kidney Int. 2005, 68, 695–703. [Google Scholar] [CrossRef] [Green Version]
- Liu, M.; Ning, X.; Li, R.; Yang, Z.; Yang, X.; Sun, S.; Qian, Q. Signalling pathways involved in hypoxia-induced renal fibrosis. J. Cell. Mol. Med. 2017, 21, 1248–1259. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baumann, B.; Hayashida, T.; Liang, X.; Schnaper, H.W. Hypoxia-inducible factor-1alpha promotes glomerulosclerosis and regulates COL1A2 expression through interactions with Smad3. Kidney Int. 2016, 90, 797–808. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rozen-Zvi, B.; Hayashida, T.; Hubchak, S.C.; Hanna, C.; Platanias, L.C.; Schnaper, H.W. TGF-beta/Smad3 activates mammalian target of rapamycin complex-1 to promote collagen production by increasing HIF-1alpha expression. Am. J. Physiol. Ren. Physiol. 2013, 305, F485–F494. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Han, W.Q.; Zhu, Q.; Hu, J.; Li, P.L.; Zhang, F.; Li, N. Hypoxia-inducible factor prolyl-hydroxylase-2 mediates transforming growth factor beta 1-induced epithelial-mesenchymal transition in renal tubular cells. Biochim. Biophys. Acta 2013, 1833, 1454–1462. [Google Scholar] [CrossRef] [Green Version]
- Hanna, C.; Hubchak, S.C.; Liang, X.; Rozen-Zvi, B.; Schumacker, P.T.; Hayashida, T.; Schnaper, H.W. Hypoxia-inducible factor-2alpha and TGF-beta signaling interact to promote normoxic glomerular fibrogenesis. Am. J. Physiol. Ren. Physiol. 2013, 305, F1323–F1331. [Google Scholar] [CrossRef] [Green Version]
- Basu, R.K.; Hubchak, S.; Hayashida, T.; Runyan, C.E.; Schumacker, P.T.; Schnaper, H.W. Interdependence of HIF-1alpha and TGF-beta/Smad3 signaling in normoxic and hypoxic renal epithelial cell collagen expression. Am. J. Physiol. Ren. Physiol. 2011, 300, F898–F905. [Google Scholar] [CrossRef] [Green Version]
- Luo, R.; Zhang, W.; Zhao, C.; Zhang, Y.; Wu, H.; Jin, J.; Zhang, W.; Grenz, A.; Eltzschig, H.K.; Tao, L.; et al. Elevated Endothelial Hypoxia-Inducible Factor-1alpha Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease. Hypertension 2015, 66, 75–84. [Google Scholar] [CrossRef] [Green Version]
- Zhang, L.; Liu, L.; Bai, M.; Liu, M.; Wei, L.; Yang, Z.; Qian, Q.; Ning, X.; Sun, S. Hypoxia-induced HE4 in tubular epithelial cells promotes extracellular matrix accumulation and renal fibrosis via NF-kappaB. FASEB J. 2020, 34, 2554–2567. [Google Scholar] [CrossRef]
- Du, R.; Xia, L.; Ning, X.; Liu, L.; Sun, W.; Huang, C.; Wang, H.; Sun, S. Hypoxia-induced Bmi1 promotes renal tubular epithelial cell-mesenchymal transition and renal fibrosis via PI3K/Akt signal. Mol. Biol. Cell 2014, 25, 2650–2659. [Google Scholar] [CrossRef]
- Hsu, R.K.; Hsu, C.Y. The Role of Acute Kidney Injury in Chronic Kidney Disease. Semin. Nephrol. 2016, 36, 283–292. [Google Scholar] [CrossRef] [Green Version]
- Hukriede, N.A.; Soranno, D.E.; Sander, V.; Perreau, T.; Starr, M.C.; Yuen, P.S.T.; Siskind, L.J.; Hutchens, M.P.; Davidson, A.J.; Burmeister, D.M.; et al. Experimental models of acute kidney injury for translational research. Nat. Rev. Nephrol. 2022, 18, 277–293. [Google Scholar] [CrossRef]
- Rosenberger, C.; Heyman, S.N.; Rosen, S.; Shina, A.; Goldfarb, M.; Griethe, W.; Frei, U.; Reinke, P.; Bachmann, S.; Eckardt, K.U. Up-regulation of HIF in experimental acute renal failure: Evidence for a protective transcriptional response to hypoxia. Kidney Int. 2005, 67, 531–542. [Google Scholar] [CrossRef] [Green Version]
- Rosenberger, C.; Pratschke, J.; Rudolph, B.; Heyman, S.N.; Schindler, R.; Babel, N.; Eckardt, K.U.; Frei, U.; Rosen, S.; Reinke, P. Immunohistochemical detection of hypoxia-inducible factor-1alpha in human renal allograft biopsies. J. Am. Soc. Nephrol. 2007, 18, 343–351. [Google Scholar] [CrossRef] [Green Version]
- Mayer, G. Capillary rarefaction, hypoxia, VEGF and angiogenesis in chronic renal disease. Nephrol. Dial. Transplant. 2011, 26, 1132–1137. [Google Scholar] [CrossRef] [Green Version]
- Mattot, V.; Moons, L.; Lupu, F.; Chernavvsky, D.; Gomez, R.A.; Collen, D.; Carmeliet, P. Loss of the VEGF(164) and VEGF(188) isoforms impairs postnatal glomerular angiogenesis and renal arteriogenesis in mice. J. Am. Soc. Nephrol. 2002, 13, 1548–1560. [Google Scholar] [CrossRef] [Green Version]
- Kang, D.H.; Joly, A.H.; Oh, S.W.; Hugo, C.; Kerjaschki, D.; Gordon, K.L.; Mazzali, M.; Jefferson, J.A.; Hughes, J.; Madsen, K.M.; et al. Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1. J. Am. Soc. Nephrol. 2001, 12, 1434–1447. [Google Scholar] [CrossRef]
- Maciel, T.T.; Coutinho, E.L.; Soares, D.; Achar, E.; Schor, N.; Bellini, M.H. Endostatin, an antiangiogenic protein, is expressed in the unilateral ureteral obstruction mice model. J. Nephrol. 2008, 21, 753–760. [Google Scholar]
- Goligorsky, M.S.; Yasuda, K.; Ratliff, B. Dysfunctional endothelial progenitor cells in chronic kidney disease. J. Am. Soc. Nephrol. 2010, 21, 911–919. [Google Scholar] [CrossRef]
- Kramann, R.; Wongboonsin, J.; Chang-Panesso, M.; Machado, F.G.; Humphreys, B.D. Gli1(+) Pericyte Loss Induces Capillary Rarefaction and Proximal Tubular Injury. J. Am. Soc. Nephrol. 2017, 28, 776–784. [Google Scholar] [CrossRef]
- Ascon, M.; Ascon, D.B.; Liu, M.; Cheadle, C.; Sarkar, C.; Racusen, L.; Hassoun, H.T.; Rabb, H. Renal ischemia-reperfusion leads to long term infiltration of activated and effector-memory T lymphocytes. Kidney Int. 2009, 75, 526–535. [Google Scholar] [CrossRef] [Green Version]
- Kong, T.; Eltzschig, H.K.; Karhausen, J.; Colgan, S.P.; Shelley, C.S. Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction of beta2 integrin gene expression. Proc. Natl. Acad. Sci. USA 2004, 101, 10440–10445. [Google Scholar] [CrossRef]
- Friederich-Persson, M.; Thorn, E.; Hansell, P.; Nangaku, M.; Levin, M.; Palm, F. Kidney hypoxia, attributable to increased oxygen consumption, induces nephropathy independently of hyperglycemia and oxidative stress. Hypertension 2013, 62, 914–919. [Google Scholar] [CrossRef] [Green Version]
- Polichnowski, A.J.; Lan, R.; Geng, H.; Griffin, K.A.; Venkatachalam, M.A.; Bidani, A.K. Severe renal mass reduction impairs recovery and promotes fibrosis after AKI. J. Am. Soc. Nephrol. 2014, 25, 1496–1507. [Google Scholar] [CrossRef] [Green Version]
- Ferenbach, D.A.; Bonventre, J.V. Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD. Nat. Rev. Nephrol. 2015, 11, 264–276. [Google Scholar] [CrossRef] [Green Version]
- Beyer, S.; Kristensen, M.M.; Jensen, K.S.; Johansen, J.V.; Staller, P. The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF. J. Biol. Chem. 2008, 283, 36542–36552. [Google Scholar] [CrossRef] [Green Version]
- Krieg, A.J.; Rankin, E.B.; Chan, D.; Razorenova, O.; Fernandez, S.; Giaccia, A.J. Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. Mol. Cell. Biol. 2010, 30, 344–353. [Google Scholar] [CrossRef] [Green Version]
- Mimura, I.; Nangaku, M.; Kanki, Y.; Tsutsumi, S.; Inoue, T.; Kohro, T.; Yamamoto, S.; Fujita, T.; Shimamura, T.; Suehiro, J.; et al. Dynamic change of chromatin conformation in response to hypoxia enhances the expression of GLUT3 (SLC2A3) by cooperative interaction of hypoxia-inducible factor 1 and KDM3A. Mol. Cell. Biol. 2012, 32, 3018–3032. [Google Scholar] [CrossRef] [Green Version]
- Rodriguez-Romo, R.; Berman, N.; Gomez, A.; Bobadilla, N.A. Epigenetic regulation in the acute kidney injury to chronic kidney disease transition. Nephrology 2015, 20, 736–743. [Google Scholar] [CrossRef]
- Zager, R.A.; Johnson, A.C.; Andress, D.; Becker, K. Progressive endothelin-1 gene activation initiates chronic/end-stage renal disease following experimental ischemic/reperfusion injury. Kidney Int. 2013, 84, 703–712. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hill, P.; Shukla, D.; Tran, M.G.; Aragones, J.; Cook, H.T.; Carmeliet, P.; Maxwell, P.H. Inhibition of hypoxia inducible factor hydroxylases protects against renal ischemia-reperfusion injury. J. Am. Soc. Nephrol. 2008, 19, 39–46. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thomas, J.L.; Pham, H.; Li, Y.; Hall, E.; Perkins, G.A.; Ali, S.S.; Patel, H.H.; Singh, P. Hypoxia-inducible factor-1alpha activation improves renal oxygenation and mitochondrial function in early chronic kidney disease. Am. J. Physiol. Ren. Physiol. 2017, 313, F282–F290. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kato, S.; Takahashi, T.; Miyata, N.; Roman, R.J. DMOG, a Prolyl Hydroxylase Inhibitor, Increases Hemoglobin Levels without Exacerbating Hypertension and Renal Injury in Salt-Sensitive Hypertensive Rats. J. Pharmacol. Exp. Ther. 2020, 372, 166–174. [Google Scholar] [CrossRef]
- Nordquist, L.; Friederich-Persson, M.; Fasching, A.; Liss, P.; Shoji, K.; Nangaku, M.; Hansell, P.; Palm, F. Activation of hypoxia-inducible factors prevents diabetic nephropathy. J. Am. Soc. Nephrol. 2015, 26, 328–338. [Google Scholar] [CrossRef] [Green Version]
- Tanaka, T.; Matsumoto, M.; Inagi, R.; Miyata, T.; Kojima, I.; Ohse, T.; Fujita, T.; Nangaku, M. Induction of protective genes by cobalt ameliorates tubulointerstitial injury in the progressive Thy1 nephritis. Kidney Int. 2005, 68, 2714–2725. [Google Scholar] [CrossRef] [Green Version]
- Ohtomo, S.; Nangaku, M.; Izuhara, Y.; Takizawa, S.; Strihou, C.; Miyata, T. Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model. Nephrol. Dial. Transplant. 2008, 23, 1166–1172. [Google Scholar] [CrossRef] [Green Version]
- Akizawa, T.; Iwasaki, M.; Yamaguchi, Y.; Majikawa, Y.; Reusch, M. Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan. J. Am. Soc. Nephrol. 2020, 31, 1628–1639. [Google Scholar] [CrossRef]
- Dhillon, S. Daprodustat: First Approval. Drugs 2020, 80, 1491–1497. [Google Scholar] [CrossRef]
- Markham, A. Vadadustat: First Approval. Drugs 2020, 80, 1365–1371. [Google Scholar] [CrossRef]
- Markham, A. Enarodustat: First Approval. Drugs 2021, 81, 169–174. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Lan, J.; Dong, F.; Duan, P. Effectiveness of hypoxia-induced factor prolyl hydroxylase inhibitor for managing anemia in chronic kidney disease: A systematic review and meta-analysis. Eur. J. Clin. Pharmacol. 2021, 77, 491–507. [Google Scholar] [CrossRef] [PubMed]
- Flight, M.H. Deal watch: AstraZeneca bets on FibroGen’s anaemia drug. Nat. Rev. Drug Discov. 2013, 12, 730. [Google Scholar] [CrossRef] [PubMed]
- Takkavatakarn, K.; Thammathiwat, T.; Phannajit, J.; Katavetin, P.; Praditpornsilpa, K.; Eiam-Ong, S.; Susantitaphong, P. The impacts of hypoxia-inducible factor stabilizers on laboratory parameters and clinical outcomes in chronic kidney disease patients with renal anemia: A systematic review and meta-analysis. Clin. Kidney J. 2023, 16, 845–858. [Google Scholar] [CrossRef]
- Sugahara, M.; Tanaka, S.; Tanaka, T.; Saito, H.; Ishimoto, Y.; Wakashima, T.; Ueda, M.; Fukui, K.; Shimizu, A.; Inagi, R.; et al. Prolyl Hydroxylase Domain Inhibitor Protects against Metabolic Disorders and Associated Kidney Disease in Obese Type 2 Diabetic Mice. J. Am. Soc. Nephrol. 2020, 31, 560–577. [Google Scholar] [CrossRef]
- Uchida, L.; Tanaka, T.; Saito, H.; Sugahara, M.; Wakashima, T.; Fukui, K.; Nangaku, M. Effects of a prolyl hydroxylase inhibitor on kidney and cardiovascular complications in a rat model of chronic kidney disease. Am. J. Physiol. Ren. Physiol. 2020, 318, F388–F401. [Google Scholar] [CrossRef]
- Yu, X.; Fang, Y.; Liu, H.; Zhu, J.; Zou, J.; Xu, X.; Jiang, S.; Ding, X. The balance of beneficial and deleterious effects of hypoxia-inducible factor activation by prolyl hydroxylase inhibitor in rat remnant kidney depends on the timing of administration. Nephrol. Dial. Transplant. 2012, 27, 3110–3119. [Google Scholar] [CrossRef] [Green Version]
- Schley, G.; Klanke, B.; Kalucka, J.; Schatz, V.; Daniel, C.; Mayer, M.; Goppelt-Struebe, M.; Herrmann, M.; Thorsteinsdottir, M.; Palsson, R.; et al. Mononuclear phagocytes orchestrate prolyl hydroxylase inhibition-mediated renoprotection in chronic tubulointerstitial nephritis. Kidney Int. 2019, 96, 378–396. [Google Scholar] [CrossRef]
- Kimura, K.; Iwano, M.; Higgins, D.F.; Yamaguchi, Y.; Nakatani, K.; Harada, K.; Kubo, A.; Akai, Y.; Rankin, E.B.; Neilson, E.G.; et al. Stable expression of HIF-1alpha in tubular epithelial cells promotes interstitial fibrosis. Am. J. Physiol. Ren. Physiol. 2008, 295, F1023–F1029. [Google Scholar] [CrossRef] [Green Version]
- Schietke, R.E.; Hackenbeck, T.; Tran, M.; Gunther, R.; Klanke, B.; Warnecke, C.L.; Knaup, K.X.; Shukla, D.; Rosenberger, C.; Koesters, R.; et al. Renal tubular HIF-2alpha expression requires VHL inactivation and causes fibrosis and cysts. PLoS ONE 2012, 7, e31034. [Google Scholar] [CrossRef] [Green Version]
- Leonard, E.C.; Friedrich, J.L.; Basile, D.P. VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury. Am. J. Physiol. Ren. Physiol. 2008, 295, F1648–F1657. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jung, Y.J.; Kim, D.H.; Lee, A.S.; Lee, S.; Kang, K.P.; Lee, S.Y.; Jang, K.Y.; Sung, M.J.; Park, S.K.; Kim, W. Peritubular capillary preservation with COMP-angiopoietin-1 decreases ischemia-reperfusion-induced acute kidney injury. Am. J. Physiol. Ren. Physiol. 2009, 297, F952–F960. [Google Scholar] [CrossRef] [Green Version]
- Engel, J.E.; Williams, E.; Williams, M.L.; Bidwell, G.L., 3rd; Chade, A.R. Targeted VEGF (Vascular Endothelial Growth Factor) Therapy Induces Long-Term Renal Recovery in Chronic Kidney Disease via Macrophage Polarization. Hypertension 2019, 74, 1113–1123. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Gobe, G. Protein kinase C activation and its role in kidney disease. Nephrology 2006, 11, 428–434. [Google Scholar] [CrossRef] [PubMed]
- Xue, X.; Ren, J.; Sun, X.; Gui, Y.; Feng, Y.; Shu, B.; Wei, W.; Lu, Q.; Liang, Y.; He, W.; et al. Protein kinase Calpha drives fibroblast activation and kidney fibrosis by stimulating autophagic flux. J. Biol. Chem. 2018, 293, 11119–11130. [Google Scholar] [CrossRef] [Green Version]
- Park, C.H.; Yoo, T.H. TGF-beta Inhibitors for Therapeutic Management of Kidney Fibrosis. Pharmaceuticals 2022, 15, 1485. [Google Scholar] [CrossRef]
- Vallon, V.; Verma, S. Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function. Annu. Rev. Physiol. 2021, 83, 503–528. [Google Scholar] [CrossRef]
- Marathias, K.P.; Lambadiari, V.A.; Markakis, K.P.; Vlahakos, V.D.; Bacharaki, D.; Raptis, A.E.; Dimitriadis, G.D.; Vlahakos, D.V. Competing Effects of Renin Angiotensin System Blockade and Sodium-Glucose Cotransporter-2 Inhibitors on Erythropoietin Secretion in Diabetes. Am. J. Nephrol. 2020, 51, 349–356. [Google Scholar] [CrossRef]
- Layton, A.T.; Vallon, V.; Edwards, A. Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron. Am. J. Physiol. Ren. Physiol. 2016, 310, F1269–F1283. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Y.; Nakano, D.; Guan, Y.; Hitomi, H.; Uemura, A.; Masaki, T.; Kobara, H.; Sugaya, T.; Nishiyama, A. A sodium-glucose cotransporter 2 inhibitor attenuates renal capillary injury and fibrosis by a vascular endothelial growth factor-dependent pathway after renal injury in mice. Kidney Int. 2018, 94, 524–535. [Google Scholar] [CrossRef] [Green Version]
- Zuo, N.; Zheng, X.; Liu, H.; Ma, X. Fenofibrate, a PPARalpha agonist, protect proximal tubular cells from albumin-bound fatty acids induced apoptosis via the activation of NF-kB. Int. J. Clin. Exp. Pathol. 2015, 8, 10653–10661. [Google Scholar]
- Tanaka, Y.; Kume, S.; Araki, S.; Isshiki, K.; Chin-Kanasaki, M.; Sakaguchi, M.; Sugimoto, T.; Koya, D.; Haneda, M.; Kashiwagi, A.; et al. Fenofibrate, a PPARalpha agonist, has renoprotective effects in mice by enhancing renal lipolysis. Kidney Int. 2011, 79, 871–882. [Google Scholar] [CrossRef] [Green Version]
- Clark, A.J.; Parikh, S.M. Targeting energy pathways in kidney disease: The roles of sirtuins, AMPK, and PGC1alpha. Kidney Int. 2021, 99, 828–840. [Google Scholar] [CrossRef] [PubMed]
- Xu, S.; Gao, Y.; Zhang, Q.; Wei, S.; Chen, Z.; Dai, X.; Zeng, Z.; Zhao, K.S. SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model. Oxidative Med. Cell. Longev. 2016, 2016, 7296092. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hong, Y.A.; Bae, S.Y.; Ahn, S.Y.; Kim, J.; Kwon, Y.J.; Jung, W.Y.; Ko, G.J. Resveratrol Ameliorates Contrast Induced Nephropathy Through the Activation of SIRT1-PGC-1alpha-Foxo1 Signaling in Mice. Kidney Blood Press. Res. 2017, 42, 641–653. [Google Scholar] [CrossRef]
- Perry, H.M.; Huang, L.; Wilson, R.J.; Bajwa, A.; Sesaki, H.; Yan, Z.; Rosin, D.L.; Kashatus, D.F.; Okusa, M.D. Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI. J. Am. Soc. Nephrol. 2018, 29, 194–206. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qi, J.; Xue, Q.; Kuang, L.; Xie, L.; Luo, R.; Nie, X. Berberine alleviates cisplatin-induced acute kidney injury by regulating mitophagy via PINK 1/Parkin pathway. Transl. Androl. Urol. 2020, 9, 1712–1724. [Google Scholar] [CrossRef] [PubMed]
- Birk, A.V.; Liu, S.; Soong, Y.; Mills, W.; Singh, P.; Warren, J.D.; Seshan, S.V.; Pardee, J.D.; Szeto, H.H. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J. Am. Soc. Nephrol. 2013, 24, 1250–1261. [Google Scholar] [CrossRef] [Green Version]
- Szeto, H.H.; Liu, S.; Soong, Y.; Wu, D.; Darrah, S.F.; Cheng, F.Y.; Zhao, Z.; Ganger, M.; Tow, C.Y.; Seshan, S.V. Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury. J. Am. Soc. Nephrol. 2011, 22, 1041–1052. [Google Scholar] [CrossRef] [Green Version]
- Stoker, M.L.; Newport, E.; Hulit, J.C.; West, A.P.; Morten, K.J. Impact of pharmacological agents on mitochondrial function: A growing opportunity? Biochem. Soc. Trans. 2019, 47, 1757–1772. [Google Scholar] [CrossRef] [Green Version]
- Ngo, V.; Duennwald, M.L. Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease. Antioxidants 2022, 11, 2345. [Google Scholar] [CrossRef] [PubMed]
- Kanda, H.; Yamawaki, K. Bardoxolone methyl: Drug development for diabetic kidney disease. Clin. Exp. Nephrol. 2020, 24, 857–864. [Google Scholar] [CrossRef] [PubMed]
- Pisano, A.; Cernaro, V.; Gembillo, G.; D’Arrigo, G.; Buemi, M.; Bolignano, D. Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2017, 18, 2283. [Google Scholar] [CrossRef] [Green Version]
- Goicoechea, M.; de Vinuesa, S.G.; Verdalles, U.; Ruiz-Caro, C.; Ampuero, J.; Rincon, A.; Arroyo, D.; Luno, J. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin. J. Am. Soc. Nephrol. 2010, 5, 1388–1393. [Google Scholar] [CrossRef] [Green Version]
- Sedeek, M.; Nasrallah, R.; Touyz, R.M.; Hebert, R.L. NADPH oxidases, reactive oxygen species, and the kidney: Friend and foe. J. Am. Soc. Nephrol. 2013, 24, 1512–1518. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kwon, G.; Uddin, M.J.; Lee, G.; Jiang, S.; Cho, A.; Lee, J.H.; Lee, S.R.; Bae, Y.S.; Moon, S.H.; Lee, S.J.; et al. A novel pan-Nox inhibitor, APX-115, protects kidney injury in streptozotocin-induced diabetic mice: Possible role of peroxisomal and mitochondrial biogenesis. Oncotarget 2017, 8, 74217–74232. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jha, J.C.; Gray, S.P.; Barit, D.; Okabe, J.; El-Osta, A.; Namikoshi, T.; Thallas-Bonke, V.; Wingler, K.; Szyndralewiez, C.; Heitz, F.; et al. Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long-term diabetic nephropathy. J. Am. Soc. Nephrol. 2014, 25, 1237–1254. [Google Scholar] [CrossRef] [Green Version]
- Sedeek, M.; Callera, G.; Montezano, A.; Gutsol, A.; Heitz, F.; Szyndralewiez, C.; Page, P.; Kennedy, C.R.; Burns, K.D.; Touyz, R.M.; et al. Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: Implications in type 2 diabetic nephropathy. Am. J. Physiol. Ren. Physiol. 2010, 299, F1348–F1358. [Google Scholar] [CrossRef]
- Kurreck, A.; Gronau, F.; Alberto Vilchez, M.E.; Abels, W.; Enghard, P.; Brandl, A.; Francis, R.; Fohre, B.; Lojewski, C.; Pratschke, J.; et al. Sodium Thiosulfate Reduces Acute Kidney Injury in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy with Cisplatin: A Single-Center Observational Study. Ann. Surg. Oncol. 2022, 29, 152–162. [Google Scholar] [CrossRef]
- Bijarnia, R.K.; Bachtler, M.; Chandak, P.G.; van Goor, H.; Pasch, A. Sodium thiosulfate ameliorates oxidative stress and preserves renal function in hyperoxaluric rats. PLoS ONE 2015, 10, e0124881. [Google Scholar] [CrossRef]
- Rein, J. Vitamin E use in preventing coronary heart disease in patients undergoing dialysis. Mayo Clin. Proc. 2002, 77, 295. [Google Scholar] [CrossRef] [PubMed]
- Karahan, S.; Afsar, B.; Kanbay, M. Ascorbic acid: A promising agent in chronic kidney disease? Clin. Kidney J. 2018, 11, 530–531. [Google Scholar] [CrossRef] [PubMed]
- Bakhshayeshkaram, M.; Lankarani, K.B.; Mirhosseini, N.; Tabrizi, R.; Akbari, M.; Dabbaghmanesh, M.H.; Asemi, Z. The Effects of Coenzyme Q10 Supplementation on Metabolic Profiles of Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Curr. Pharm. Des. 2018, 24, 3710–3723. [Google Scholar] [CrossRef]
- Dare, A.J.; Bolton, E.A.; Pettigrew, G.J.; Bradley, J.A.; Saeb-Parsy, K.; Murphy, M.P. Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ. Redox Biol. 2015, 5, 163–168. [Google Scholar] [CrossRef] [Green Version]
- Zhu, Z.; Liang, W.; Chen, Z.; Hu, J.; Feng, J.; Cao, Y.; Ma, Y.; Ding, G. Mitoquinone Protects Podocytes from Angiotensin II-Induced Mitochondrial Dysfunction and Injury via the Keap1-Nrf2 Signaling Pathway. Oxidative Med. Cell. Longev. 2021, 2021, 1394486. [Google Scholar] [CrossRef] [PubMed]
- Ashkar, F.; Bhullar, K.S.; Wu, J. The Effect of Polyphenols on Kidney Disease: Targeting Mitochondria. Nutrients 2022, 14, 3115. [Google Scholar] [CrossRef]
- Rassaf, T.; Rammos, C.; Hendgen-Cotta, U.B.; Heiss, C.; Kleophas, W.; Dellanna, F.; Floege, J.; Hetzel, G.R.; Kelm, M. Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double-Blind, Randomized, Placebo-Controlled Trial. Clin. J. Am. Soc. Nephrol. 2016, 11, 108–118. [Google Scholar] [CrossRef] [Green Version]
- Ullah, M.M.; Basile, D.P. Role of Renal Hypoxia in the Progression From Acute Kidney Injury to Chronic Kidney Disease. Semin. Nephrol. 2019, 39, 567–580. [Google Scholar] [CrossRef]
- Tanaka, S.; Tanaka, T.; Nangaku, M. Hypoxia and hypoxia-inducible factors in chronic kidney disease. Ren. Replace. Ther. 2016, 2, 25. [Google Scholar] [CrossRef] [Green Version]
- Tanaka, T.; Kojima, I.; Ohse, T.; Ingelfinger, J.R.; Adler, S.; Fujita, T.; Nangaku, M. Cobalt promotes angiogenesis via hypoxia-inducible factor and protects tubulointerstitium in the remnant kidney model. Lab. Investig. 2005, 85, 1292–1307. [Google Scholar] [CrossRef] [Green Version]
- Deng, A.; Arndt, M.A.; Satriano, J.; Singh, P.; Rieg, T.; Thomson, S.; Tang, T.; Blantz, R.C. Renal protection in chronic kidney disease: Hypoxia-inducible factor activation vs. angiotensin II blockade. Am. J. Physiol. Ren. Physiol. 2010, 299, F1365–F1373. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dallatu, M.K.; Nwokocha, E.; Agu, N.; Myung, C.; Newaz, M.A.; Garcia, G.; Truong, L.D.; Oyekan, A.O. The Role of Hypox-ia-Inducible Factor/Prolyl Hydroxylation Pathway in Deoxycorticosterone Acetate/Salt Hypertension in the Rat. J. Hypertens. 2014, 3, 184. [Google Scholar] [CrossRef]
- Ikeda, Y.; Ozono, I.; Tajima, S.; Imao, M.; Horinouchi, Y.; Izawa-Ishizawa, Y.; Kihira, Y.; Miyamoto, L.; Ishizawa, K.; Tsuchi-ya, K.; et al. Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction. PLoS ONE 2014, 9, e89355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nayak, B.K.; Shanmugasundaram, K.; Friedrichs, W.E.; Cavaglierii, R.C.; Patel, M.; Barnes, J.; Block, K. HIF-1 Mediates Renal Fibrosis in OVE26 Type 1 Diabetic Mice. Diabetes 2016, 65, 1387–1397. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, X.; Liang, D.; Fan, J.; Lian, X.; Zhao, Y.; Wang, X.; Chi, Z.H.; Zhang, P. Zinc Attenuates Tubulointerstitial Fibrosis in Diabetic Nephropathy Via Inhibition of HIF Through PI-3K Signaling. Biol. Trace Elem. Res. 2016, 173, 372–383. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Miguel, V.; Rojo, A. Hypoxia-Driven Responses in Chronic Kidney Disease. Oxygen 2023, 3, 300-321. https://doi.org/10.3390/oxygen3030020
Miguel V, Rojo A. Hypoxia-Driven Responses in Chronic Kidney Disease. Oxygen. 2023; 3(3):300-321. https://doi.org/10.3390/oxygen3030020
Chicago/Turabian StyleMiguel, Verónica, and Alba Rojo. 2023. "Hypoxia-Driven Responses in Chronic Kidney Disease" Oxygen 3, no. 3: 300-321. https://doi.org/10.3390/oxygen3030020
APA StyleMiguel, V., & Rojo, A. (2023). Hypoxia-Driven Responses in Chronic Kidney Disease. Oxygen, 3(3), 300-321. https://doi.org/10.3390/oxygen3030020