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- Title
Endothelial cell-derived endothelin-1 is involved in abnormal scar formation by dermal fibroblasts through RhoA/Rho-kinase pathway.
- Authors
Kiya, Koichiro; Kubo, Tateki; Kawai, Kenichiro; Matsuzaki, Shinsuke; Maeda, Daisuke; Fujiwara, Toshihiro; Nishibayashi, Akimitsu; Kanazawa, Shigeyuki; Yano, Kenji; Amano, Genki; Katayama, Taiichi; Hosokawa, Ko
- Abstract
Hypertrophic scars and keloids are characterized by excessive dermal deposition of extracellular matrix due to fibroblast-to-myofibroblast differentiation. Endothelin-1 ( ET-1) is primarily produced by vascular endothelial cells and plays multiple roles in the wound-healing response and organ fibrogenesis. In this study, we investigated the pathophysiological significance of ET-1 and involvement of RhoA, a member of the Rho GTPases, in hypertrophic scar/keloid formation. We found that ET-1 expression on dermal microvascular endothelial cells ( ECs) in hypertrophic scars and keloids was higher than that in normal skin and mature scars. We also confirmed that ET-1 induced myofibroblast differentiation and collagen synthesis in cultured human dermal fibroblasts through the RhoA/Rho-kinase pathway. Finally, since hypertrophic scar/keloid formation was most prominent in areas exposed to mechanical stretch, we examined how mechanical stretch affected ET-1 secretion in human dermal microvascular ECs, and found that mechanical stretch increased ET-1 gene expression and secretion from ECs. Taken together, these results suggest that dermal microvascular ECs release ET-1 in response to mechanical stretch, and thereby contribute to the formation of hypertrophic scars and keloids through the RhoA/Rho-kinase pathway.
- Subjects
HYPERTROPHIC scars; KELOIDS; PREPROENDOTHELIN; ENDOTHELIAL cells; GENE expression
- Publication
Experimental Dermatology, 2017, Vol 26, Issue 8, p705
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.13264