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Hypoxia and HIF-1α Regulate Collagen Production in Keloids

Authors
 Yuanyuan Kang  ;  Mi Ryung Roh  ;  Suvi Rajadurai  ;  Anpuchchelvi Rajadurai  ;  Raj Kumar  ;  Ching-Ni Njauw  ;  Zhenlong Zheng  ;  Hensin Tsao 
Citation
 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol.140(11) : 2157-2165, 2020-11 
Journal Title
 JOURNAL OF INVESTIGATIVE DERMATOLOGY 
ISSN
 0022-202X 
Issue Date
2020-11
Abstract
Keloids are reactive or spontaneous fibroproliferative dermal tumors characterized by the exaggerated and uncontrolled accumulation of extracellular collagen. Current approaches to mitigate keloidogenesis are largely procedural in nature. However, a better understanding of its biological drivers may lead to novel targeted treatments for keloids. Through whole-genome expression analysis, we found that an HIF-1α transcriptional footprint is preferentially upregulated (activation score = 2.024; P = 1.05E-19) in keloid fibroblasts compared with normal dermal fibroblasts. We verified that HIF-1α protein is more strongly expressed in keloid specimens compared with normal skin (P = 0.035) and that hypoxia (1% O2) leads to increased collagen, especially in the extracellular compartment. Collagen levels were reduced uniformly by selective HIF-1α inhibitor CAY10585. Our results indicate that collagen secretion may be intimately linked to a hypoxic microenvironment within keloid tumors and that HIF-1α blockade could be a novel avenue of treatment for these tumors.
Full Text
https://www.sciencedirect.com/science/article/pii/S0022202X20313506
DOI
10.1016/j.jid.2020.01.036
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Roh, Mi Ryung(노미령) ORCID logo https://orcid.org/0000-0002-6285-2490
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180527
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