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- Title
Hypoxia-Induced Epithelial-To-Mesenchymal Transition Mediates Fibroblast Abnormalities via EKR Activation in Cutaneous Wound Healing.
- Authors
Kim, Jihee; Kim, Bomi; Kim, Soo Min; Yang, Chae Eun; Song, Seung Yong; Lee, Won Jai; Lee, Ju Hee
- Abstract
Previous studies described the involvement of extracellular signal-related kinase (ERK) in systemic fibrotic diseases, but the role of ERK in cutaneous scarring is unknown. Although hypoxia drives tissue fibrosis by activating hypoxia-inducible factor-1α (HIF-1α), the specific roles of hypoxia and associated ERK phosphorylation in abnormal fibroblast activity during cutaneous scarring are unclear. Here, we investigated whether pathologic myofibroblast-like keloid fibroblast activity is promoted by hypoxia-induced epithelial–mesenchymal transition mediated by ERK activation. ERK phosphorylation was significantly increased in keloid tissue and fibroblasts. Human dermal fibroblasts cultured under hypoxia (1% O2) expressed phosphorylated ERK and exhibited activation of p38 mitogen-activated protein kinase signaling. Hypoxic human dermal fibroblasts showed increased protein and mRNA levels of epithelial–mesenchymal transition markers. Furthermore, administration of an ERK inhibitor (SCH772984) reduced the hypoxia-induced elevation of collagen type I levels in human dermal fibroblasts. Therefore, ERK may be a promising therapeutic target in profibrogenic diseases.
- Subjects
FIBROBLASTS; EXTRACELLULAR signal-regulated kinases; PHOSPHORYLATION; WOUND healing; COLLAGEN
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 10, p2546
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20102546