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.
Bibliographical noteFunding 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).
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). Conceptualization: YK, MRR, HT; Data Curation: YK, MRR, HT; Formal Analysis: YK, MRR, SR, HT; Funding Acquisition: MRR, HT; Investigation: YK, MRR, RK, AR, CN, ZZ; Methodology: YK, MRR, HT; Project Administration: HT; Supervision: HT; Validation: YK, MRR; Visualization: YK, MRR, HT; Writing - Original Draft Preparation: YK, MRR, AR, RK, HT; Writing - Review and Editing: YK, HT
© 2020 The Authors
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology