ProBDNF Upregulation in Murine Hind Limb Ischemia Reperfusion Injury: A Driver of Inflammation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. BDNF Exon VI Splice Variant Is Expressed by Skeletal Muscle
3.2. Comparison of BDNF Protein Levels in Skeletal Muscle and Brain
3.3. Comparison of the Levels of Proprotein Convertases in Skeletal Muscle and Brain
3.4. BDNF Is More Highly Expressed in Young Developing Skeletal Muscle
3.5. IR Injury Significantly Upregulates ProBDNF in Injured Tissue
3.6. IR-injured Muscle Induces a Significant Inflammatory Response
3.7. Skeletal Muscle-Specific Knockout of BDNF Attenuates Proinflammatory Response following IR Injury
3.8. p75NTR Inhibition Attenuates the Proinflammatory Response following IR Injury
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Foltran, R.B.; Diaz, S.L. BDNF isoforms: A round trip ticket between neurogenesis and serotonin? J. Neurochem. 2016, 138, 204–221. [Google Scholar] [CrossRef] [Green Version]
- Luo, C.; Zhong, X.-L.; Zhou, F.H.; Li, J.-Y.; Zhou, P.; Xu, J.-M.; Song, B.; Li, C.-Q.; Zhou, X.-F.; Dai, R.-P. Peripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator. Sci Rep. 2016, 6, 27171. [Google Scholar] [CrossRef] [PubMed]
- Pedersen, B.K.; Pedersen, M.; Krabbe, K.S.; Bruunsgaard, H.; Matthews, V.B.; Febbraio, M.A. Role of exercise-induced brain-derived neurotrophic factor production in the regulation of energy homeostasis in mammals. Exp Physiol. 2009, 94, 1153–1160. [Google Scholar] [CrossRef]
- Clow, C.; Jasmin, B.J. Brain-derived neurotrophic factor regulates satellite cell differentiation and skeltal muscle regeneration. Mol. Biol. Cell 2010, 21, 2182–2190. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Colombo, E.; Bedogni, F.; Lorenzetti, I.; Landsberger, N.; Previtali, S.C.; Farina, C. Autocrine and immune cell-derived BDNF in human skeletal muscle: Implications for myogenesis and tissue regeneration. J. Pathol. 2013, 231, 190–198. [Google Scholar] [CrossRef]
- Iu, E.C.Y.; Chan, C.B. Is Brain-Derived Neurotrophic Factor a Metabolic Hormone in Peripheral Tissues? Biology 2022, 11, 1063. [Google Scholar] [CrossRef] [PubMed]
- Schnyder, S.; Handschin, C. Skeletal muscle as an endocrine organ: PGC-1alpha, myokines and exercise. Bone 2015, 80, 115–125. [Google Scholar] [CrossRef] [Green Version]
- Chao, M.V.a.M.B. Neurotophins: To Cleave or not to Cleave. Neuron 2002, 33, 4. [Google Scholar]
- Barker, P.A. Whither proBDNF? Nat. Neurosci. 2009, 12, 3. [Google Scholar] [CrossRef]
- Koshimizu, H.; Hazama, S.; Hara, T.; Ogura, A.; Kojima, M. Distinct signaling pathways of precursor BDNF and mature BDNF in cultured cerebellar granule neurons. Neurosci. Lett. 2010, 473, 229–232. [Google Scholar] [CrossRef]
- Hing, B.; Sathyaputri, L.; Potash, J.B. A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2018, 177, 143–167. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pang, P.T.; Teng, H.K.; Zaitsev, E.; Woo, N.T.; Sakata, K.; Zhen, S.; Teng, K.K.; Yung, W.-H.; Hempstead, B.L.; Lu, B. Cleavage of proBDNF by tPA/Plasmin is essential for long-term hippocampal plasticity. Science 2004, 306, 487–491. [Google Scholar] [CrossRef] [PubMed]
- Mowla, S.J.; Farhadi, H.F.; Pareek, S.; Atwal, J.K.; Morris, S.J.; Seidah, N.G.; Murphy, R.A. Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor. J. Biol. Chem. 2001, 276, 12660–12666. [Google Scholar] [CrossRef] [Green Version]
- Brigadski, T.; Leßmann, V. The physiology of regulated BDNF release. Cell Tissue Res. 2020, 382, 15–45. [Google Scholar] [CrossRef]
- Mandel, A.; Ozdener, H.; Utermohlen, V. Identification of pro- and mature brain-derived neurotrophic factor in human saliva. Arch. Oral Biol. 2009, 54, 689–695. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, B.; Ren, Q.; Zhang, J.-C.; Chen, Q.-X.; Hashimoto, K. Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: Rethinking the brain-liver axis. Transl. Psychiatry 2017, 7, e1128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Delezie, J.; Weihrauch, M.; Maier, G.; Tejero, R.; Ham, D.J.; Gill, J.F.; Karrer-Cardel, B.; Rüegg, M.A.; Tabares, L.; Handschin, C. BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle. Proc. Natl. Acad. Sci. USA 2019, 116, 16111–16120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, J.H.; Jun, H.-S. Role of Myokines in Regulating Skeletal Muscle Mass and Function. Front. Physiol. 2019, 10, 42. [Google Scholar] [CrossRef]
- Matthews, V.B.; Åström, M.-B.; Chan, M.H.S.; Bruce, C.R.; Krabbe, K.S.; Prelovsek, O.; Åkerström, T.; Yfanti, C.; Broholm, C.; Mortensen, O.H.; et al. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia 2009, 52, 1409–1418. [Google Scholar] [CrossRef] [Green Version]
- Prats, C.; Gomez-Cabello, A.; Nordby, P.; Andersen, J.L.; Helge, J.W.; Dela, F.; Baba, O.; Ploug, T. An optimized histochemical method to assess skeletal muscle glycogen and lipid stores reveals two metabolically distinct populations of type I muscle fibers. PLoS ONE 2013, 8, e77774. [Google Scholar] [CrossRef]
- Rios, M. BDNF and the central control of feeding: Accidental bystander or essential player? Trends Neurosci. 2013, 36, 83–90. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- D’Oria, M.; Mani, K.; Lorenzo, A.R. Microsurgical Salvage of Acute Lower Limb Ischemia after Iatrogenic Femoral Injury during Orthopedic Surgery in a Pediatric Patient. Ann. Vasc. Surg. 2020, 69, 452.e5–452.e11. [Google Scholar] [CrossRef] [PubMed]
- Gillani, S.; Cao, J.; Suzuki, T.; Hak, D.J. The effect of ischemia reperfusion injury on skeletal muscle. Injury 2012, 43, 670–675. [Google Scholar] [CrossRef] [PubMed]
- Apichartpiyakul, P.; Shinlapawittayatorn, K.; Rerkasem, K.; Chattipakorn, S.C.; Chattipakorn, N. Mechanisms and Interventions on Acute Lower Limb Ischemia/Reperfusion Injury: A Review and Insights from Cell to Clinical Investigations. Ann. Vasc. Surg. 2022, 86, 452–481. [Google Scholar] [CrossRef] [PubMed]
- Chazaud, B. Inflammation and Skeletal Muscle Regeneration: Leave It to the Macrophages! Trends Immunol. 2020, 41, 481–492. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.J.; Arpino, J.-M.; Yin, H.; Nong, Z.; Szpakowski, A.; Hashi, A.A.; Chevalier, J.; O’neil, C.; Pickering, J.G. Systematic Interrogation of Angiogenesis in the Ischemic Mouse Hind Limb: Vulnerabilities and Quality Assurance. Arter. Thromb. Vasc. Biol. 2020, 40, 2454–2467. [Google Scholar] [CrossRef] [PubMed]
- Crawford, R.S.; Hashmi, F.F.; Jones, J.E.; Albadawi, H.; McCormack, M.; Eberlin, K.; Entabi, F.; Atkins, M.D.; Conrad, M.F.; Austen, W.G.; et al. A novel model of acute murine hindlimb ischemia. Am. J. Physiol. Heart Circ. Physiol. 2007, 292, H830–H837. [Google Scholar] [CrossRef] [PubMed]
- Tu, H.; Zhang, D.; Qian, J.; Barksdale, A.N.; Pipinos, I.I.; Patel, K.P.; Wadman, M.C.; Li, Y.-L. A comparison of acute mouse hindlimb injuries between tourniquet- and femoral artery ligation-induced ischemia-reperfusion. Injury 2021, 52, 3217–3226. [Google Scholar] [CrossRef]
- Elshaer, S.L.; Alwhaibi, A.; Mohamed, R.; Lemtalsi, T.; Coucha, M.; Longo, F.M.; El-Remessy, A.B. Modulation of the p75 neurotrophin receptor using LM11A-31 prevents diabetes-induced retinal vascular permeability in mice via inhibition of inflammation and the RhoA kinase pathway. Diabetologia 2019, 62, 1488–1500. [Google Scholar] [CrossRef] [Green Version]
- Malik, S.C.; Sozmen, E.G.; Baeza-Raja, B.; Le Moan, N.; Akassoglou, K.; Schachtrup, C. In vivo functions of p75(NTR): Challenges and opportunities for an emerging therapeutic target. Trends Pharmacol. Sci. 2021, 42, 772–788. [Google Scholar] [CrossRef]
- Meeker, R.; Williams, K. The p75 neurotrophin receptor: At the crossroad of neural repair and death. Neural Regen. Res. 2015, 10, 721–725. [Google Scholar] [CrossRef] [PubMed]
- Aby, K.; Antony, R.; Eichholz, M.; Srinivasan, R.; Li, Y. Enhanced pro-BDNF-p75NTR pathway activity in denervated skeletal muscle. Life Sci. 2021, 286, 120067. [Google Scholar] [CrossRef] [PubMed]
- Chopra, A.; Willmore, W.G.; Biggar, K.K. Protein quantification and visualization via ultraviolet-dependent labeling with 2,2,2-trichloroethanol. Sci. Rep. 2019, 9, 13923. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aid, T.; Kazantseva, A.; Piirsoo, M.; Palm, K.; Timmusk, T. Mouse and rat BDNF gene structure and expression revisited. J. Neurosci. Res. 2007, 85, 525–535. [Google Scholar] [CrossRef] [PubMed]
- Keifer, J. Comparative Genomics of the BDNF Gene, Non-Canonical Modes of Transcriptional Regulation, and Neurological Disease. Mol. Neurobiol. 2021, 58, 2851–2861. [Google Scholar] [CrossRef]
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Aby, K.; Antony, R.; Li, Y. ProBDNF Upregulation in Murine Hind Limb Ischemia Reperfusion Injury: A Driver of Inflammation. Biology 2023, 12, 903. https://doi.org/10.3390/biology12070903
Aby K, Antony R, Li Y. ProBDNF Upregulation in Murine Hind Limb Ischemia Reperfusion Injury: A Driver of Inflammation. Biology. 2023; 12(7):903. https://doi.org/10.3390/biology12070903
Chicago/Turabian StyleAby, Katherine, Ryan Antony, and Yifan Li. 2023. "ProBDNF Upregulation in Murine Hind Limb Ischemia Reperfusion Injury: A Driver of Inflammation" Biology 12, no. 7: 903. https://doi.org/10.3390/biology12070903