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 journalArticle

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
JournalJournal of Investigative Dermatology
DOIs
Publication statusAccepted/In press - 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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  • Cite this

    Kang, Y., Roh, M. R., Rajadurai, S., Rajadurai, A., Kumar, R., Njauw, C. N., Zheng, Z., & Tsao, H. (Accepted/In press). Hypoxia and HIF-1α Regulate Collagen Production in Keloids. Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2020.01.036