» Articles » PMID: 28611671

Targeting Hypoxia Inducible Factors-1α As a Novel Therapy in Fibrosis

Overview
Journal Front Pharmacol
Date 2017 Jun 15
PMID 28611671
Citations 42
Authors
Affiliations
Soon will be listed here.
Abstract

Fibrosis, characterized by increased extracellular matrix (ECM) deposition, and widespread vasculopathy, has the prominent trait of chronic hypoxia. Hypoxia inducible factors-1α (HIF-1α), a key transcriptional factor in response to this chronic hypoxia, is involved in fibrotic disease, such as Systemic sclerosis (SSc). The implicated function of HIF-1α in fibrosis include stimulation of excessive ECM, vascular remodeling, and futile angiogenesis with further exacerbation of chronic hypoxia and deteriorate pathofibrogenesis. This review will focus on the molecular biological behavior of HIF-1α in regulating progressive fibrosis. Better understanding of the role for HIF-1α-regulated pathways in fibrotic disease will accelerate development of novel therapeutic strategies that target HIF-1α. Such new therapeutic strategies may be particularly effective for treatment of the prototypic, multisystem fibrotic, autoimmune disease SSc.

Citing Articles

miR-210 overexpression increases pressure overload-induced cardiac fibrosis.

Zaccagnini G, Baci D, Tastsoglou S, Cozza I, Made A, Voellenkle C Noncoding RNA Res. 2025; 12:20-33.

PMID: 40034123 PMC: 11874870. DOI: 10.1016/j.ncrna.2025.01.009.


The Physiological Functions and Therapeutic Potential of Hypoxia-Inducible Factor-1α in Vascular Calcification.

Zhang Z, Wang D, Xu R, Li X, Wang Z, Zhang Y Biomolecules. 2025; 14(12.

PMID: 39766299 PMC: 11674127. DOI: 10.3390/biom14121592.


High altitudes, deeper insights: multicenter cardiovascular magnetic resonance study on hypertrophic cardiomyopathy.

Chen Z, Sun Y, Yang N, Nan J, Cao L, Zhao L Eur Radiol. 2024; .

PMID: 39741217 DOI: 10.1007/s00330-024-11305-2.


A multi-omics approach identifies the key role of disorders of sphingolipid metabolism in Ang II-induced hypertensive cardiomyopathy myocardial remodeling.

Qu Y, Ma D, Wu T, Wang H, Tian Z, Liu X Sci Rep. 2024; 14(1):30379.

PMID: 39638825 PMC: 11621778. DOI: 10.1038/s41598-024-81611-8.


The role of hypoxic microenvironment in autoimmune diseases.

Gong X, Yang S, Wang Z, Tang M Front Immunol. 2024; 15:1435306.

PMID: 39575238 PMC: 11578973. DOI: 10.3389/fimmu.2024.1435306.


References
1.
Halberg N, Khan T, Trujillo M, Wernstedt-Asterholm I, Attie A, Sherwani S . Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol. 2009; 29(16):4467-83. PMC: 2725728. DOI: 10.1128/MCB.00192-09. View

2.
LeRoy E . Systemic sclerosis. A vascular perspective. Rheum Dis Clin North Am. 1996; 22(4):675-94. DOI: 10.1016/s0889-857x(05)70295-7. View

3.
Kahaleh M, Sherer G, LeRoy E . Endothelial injury in scleroderma. J Exp Med. 1979; 149(6):1326-35. PMC: 2184886. DOI: 10.1084/jem.149.6.1326. View

4.
Semenza G . Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003; 3(10):721-32. DOI: 10.1038/nrc1187. View

5.
Kim M, Kwon H, Lee Y, Baek J, Jang J, Lee S . Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med. 2001; 7(4):437-43. DOI: 10.1038/86507. View