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

International Journal of Molecular Sciences

JuHee Lee¹  Jihee Kim¹  SooMin Kim¹  Bomi Kim¹  ChaeEun Yang²  SeungYong Song³  WonJai Lee³ 

[1] Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea;Department of Plastic and Reconstructive Surgery, Yonsei University Wonju College of Medicine, Wonju 26426, Korea;Scar Laser and Plastic Surgery Center, Yonsei Cancer Hospital, Seoul 03722, Korea;

关键词: wound healing;    ERK;    hypoxia;    fibroblast;    scar;   

DOI  :  10.3390/ijms20102546

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown