Hypoxia and HIF-1α Regulate Collagen Production in Keloids

Yuanyuan Kang, Mi Ryung Roh, Suvi Rajadurai, Anpuchchelvi Rajadurai, Raj Kumar, Ching Ni Njauw, Zhenlong Zheng, Hensin Tsao

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2157-2165
Number of pages9
JournalJournal of Investigative Dermatology
Volume140
Issue number11
DOIs
Publication statusPublished - 2020 Nov

Bibliographical note

Funding Information:
This study was supported in part by the Dept of Defense Air Force Office of Scientific Research (FA9550-10-1-0537 to HT), a faculty research grant of Yonsei University College of Medicine (6-2017-0078 to MRR), and institutional funds (to HT).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint Dive into the research topics of 'Hypoxia and HIF-1α Regulate Collagen Production in Keloids'. Together they form a unique fingerprint.

Cite this