Functional Repercussions of Hypoxia-Inducible Factor-2α in Idiopathic Pulmonary Fibrosis
Abstract
:1. Introduction
2. Lung Oxygenation and Hypoxic Conditions
3. Hypoxia Changes Mediated by Hypoxia-Inducible Factors
4. Hypoxia in Physiological Processes
4.1. Lung Development
4.2. Cell Cycle
Gene | TF | Cell Cycle | Finding | References |
---|---|---|---|---|
c-Myc | HIF-1α | Arrest | Prevents the formation of complexes of Myc with its promoters and therefore the activation of its target genes | [78] |
HIF-2α | Proliferation | Promotes Myc binding to its promoters and activation of its target genes | [73] | |
p27 | HIF-1α | Arrest | HIF-dependent induction in lymphocytes by displacement of Myc to its promoters | [73,78,79] |
p21 | HIF-1α | Arrest | HIF-dependent induction in fibroblasts by displacement of Myc to its promoters. | [78,79] |
Cyclin D2 | HIF-1α | Arrest | Prevents the formation of Myc-DNA binding site complexes and alters the expression of Cyclin D2 | [78] |
ATR | HIF-1α | Arrest | Interferes with ATR activating protein and promotes ATR activation | [80] |
oct-04 | HIF-2α | Differentiation | Regulation of cell differentiation in stem cells | [73] |
miRNA 210 | HIF-1α | Arrest | HIF-1α-dependent regulation | [81,84] |
AURKA | HIF-1α | Proliferation | Cell proliferation hepatocellular carcinoma | [85] |
Decreases AURKA activity | Negative regulator of AURKA in breast cancer tumors | [86] |
4.3. Immune Response
Cell Type | HIF Activity in the Immune Response | Reference |
---|---|---|
Bacterial infections | Control of the intracellular antibacterial response by macrophages by HIF-1α | [91] |
Control of bacterial phagocytosis | [89] | |
HIF-1α-dependent antimicrobial activity in myeloid cells through nitric oxide expression | [88] | |
Macrophages | Regulation of macrophage motility, invasion, and aggregation by HIF-1α | [91] |
Polarization of M1 macrophages by HIF-1α activity secondary to TH1 induction and of M2 macrophages by HIF-2α induced by Th2 cells | [97] | |
Modulation of macrophage migration by HIF-2α regulatory activity of cytokine receptor expression | [98] | |
Neutrophils | mTOR regulates NET formation by transcriptional control of HIF-1α expression in hypoxia | [99] |
Reversible inhibition of neutrophil apoptosis by hypoxia, could be related to HIF-1α activity | [100] | |
HIF-2α regulates neutrophil apoptosis in vivo, reducing inflammation and tissue injury | [101] | |
Dendritic cells | HIF-1α and hypoxia play a role in the activation of dendritic cells in an inflammatory state | [102] |
Increased migratory capacity of dendritic cells and HIF-1α-dependent induction of IL-22 in hypoxia | [103] | |
Pharmacological certainty of HIF-1α by PDH inhibitor increases MHC, co-stimulation of molecule expression and reduction of T cells | [104] | |
HIF-1α activity on migration of dendritic cells matured in hypoxia | [105] | |
Chemokines cytokines | Regulation of expression of M-CSFR cytokine receptors and CXCR4 chemokines | [98] |
T cells | HIF-1α-dependent glycolytic metabolic switch is a checkpoint for Th17 and Treg cell proliferation | [106] |
HIF-1α is involved in downregulation of Th1 cells | [92] | |
HIF-1α is required for the regulation of glycolytic pathways, chemokine expression, and adhesion receptors that regulate CD8+ T cell trafficking | [93] | |
B Cells | HIF-1α activity in the glycolytic pathway affects B cell development and differentiation | [95] |
HIF-1α has transcriptional activity in IL-10 expression in CD1dhiCD5+ B cells and in the control of its protective activity in autoimmune diseases | [107] |
4.4. Regeneration and Repair
5. Hypoxia-Inducible Factor-2α has a Particular Response in Idiopathic Pulmonary Fibrosis Pathogenesis
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Torres-Soria, A.K.; Romero, Y.; Balderas-Martínez, Y.I.; Velázquez-Cruz, R.; Torres-Espíndola, L.M.; Camarena, A.; Flores-Soto, E.; Solís-Chagoyán, H.; Ruiz, V.; Carlos-Reyes, Á.; et al. Functional Repercussions of Hypoxia-Inducible Factor-2α in Idiopathic Pulmonary Fibrosis. Cells 2022, 11, 2938. https://doi.org/10.3390/cells11192938
Torres-Soria AK, Romero Y, Balderas-Martínez YI, Velázquez-Cruz R, Torres-Espíndola LM, Camarena A, Flores-Soto E, Solís-Chagoyán H, Ruiz V, Carlos-Reyes Á, et al. Functional Repercussions of Hypoxia-Inducible Factor-2α in Idiopathic Pulmonary Fibrosis. Cells. 2022; 11(19):2938. https://doi.org/10.3390/cells11192938
Chicago/Turabian StyleTorres-Soria, Ana Karen, Yair Romero, Yalbi I. Balderas-Martínez, Rafael Velázquez-Cruz, Luz Maria Torres-Espíndola, Angel Camarena, Edgar Flores-Soto, Héctor Solís-Chagoyán, Víctor Ruiz, Ángeles Carlos-Reyes, and et al. 2022. "Functional Repercussions of Hypoxia-Inducible Factor-2α in Idiopathic Pulmonary Fibrosis" Cells 11, no. 19: 2938. https://doi.org/10.3390/cells11192938
APA StyleTorres-Soria, A. K., Romero, Y., Balderas-Martínez, Y. I., Velázquez-Cruz, R., Torres-Espíndola, L. M., Camarena, A., Flores-Soto, E., Solís-Chagoyán, H., Ruiz, V., Carlos-Reyes, Á., Salinas-Lara, C., Luis-García, E. R., Chávez, J., Castillejos-López, M., & Aquino-Gálvez, A. (2022). Functional Repercussions of Hypoxia-Inducible Factor-2α in Idiopathic Pulmonary Fibrosis. Cells, 11(19), 2938. https://doi.org/10.3390/cells11192938