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Hypoxia-Induced Epithelial-To-Mesenchymal Transition Mediates Fibroblast Abnormalities via ERK Activation in Cutaneous Wound Healing

 Jihee Kim  ;  Bomi Kim  ;  Soo Min Kim  ;  Chae Eun Yang  ;  Seung Yong Song  ;  Won Jai Lee  ;  Ju Hee Lee 
 International Journal of Molecular Sciences, Vol.20(10) : E2546, 2019 
Journal Title
 International Journal of Molecular Sciences 
Issue Date
ERK ;  fibroblast ; hypoxia ; scar ;  wound healing
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, ERKmay be a promising therapeutic target in profibrogenic diseases.
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jihee(김지희) ORCID logo https://orcid.org/0000-0002-0047-5941
Song, Seung Yong(송승용) ORCID logo https://orcid.org/0000-0002-3145-7463
Lee, Won Jai(이원재) ORCID logo https://orcid.org/0000-0003-3056-0503
Lee, Ju Hee(이주희) ORCID logo https://orcid.org/0000-0002-1739-5956
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