Hypoxia and HIF-1α Regulate Collagen Production in Keloids
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...
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| Veröffentlicht in: | Journal of investigative dermatology 2020-11, Vol.140 (11), p.2157-2165 |
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| creator | Kang, Yuanyuan Roh, Mi Ryung Rajadurai, Suvi Rajadurai, Anpuchchelvi Kumar, Raj Njauw, Ching-Ni Zheng, Zhenlong Tsao, Hensin |
| description | 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. |
| doi_str_mv | 10.1016/j.jid.2020.01.036 |
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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.</description><identifier>ISSN: 0022-202X</identifier><identifier>EISSN: 1523-1747</identifier><identifier>DOI: 10.1016/j.jid.2020.01.036</identifier><identifier>PMID: 32315657</identifier><language>eng</language><publisher>NEW YORK: Elsevier Inc</publisher><subject>Cell Hypoxia - physiology ; Cells, Cultured ; Collagen - biosynthesis ; Dermatology ; Fibroblasts - metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors ; Hypoxia-Inducible Factor 1, alpha Subunit - physiology ; Keloid - metabolism ; Life Sciences & Biomedicine ; Science & Technology</subject><ispartof>Journal of investigative dermatology, 2020-11, Vol.140 (11), p.2157-2165</ispartof><rights>2020 The Authors</rights><rights>Copyright © 2020 The Authors. Published by Elsevier Inc. 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| subjects | Cell Hypoxia - physiology Cells, Cultured Collagen - biosynthesis Dermatology Fibroblasts - metabolism Humans Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors Hypoxia-Inducible Factor 1, alpha Subunit - physiology Keloid - metabolism Life Sciences & Biomedicine Science & Technology |
| title | Hypoxia and HIF-1α Regulate Collagen Production in Keloids |
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