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Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis.

 Won Jai Lee  ;  Ji Hun Park  ;  Jung U. Shin  ;  Hyun Noh  ;  Dae Hyun Lew  ;  Woo Ick Yang  ;  Chae Ok Yun  ;  Kwang Hoon Lee  ;  Ju Hee Lee 
 Wound Repair and Regeneration, Vol.23(3) : 435-442, 2015 
Journal Title
 Wound Repair and Regeneration 
Issue Date
Endothelial-to-mesenchymal transition is a phenotypic conversion characterized by down-regulation of vascular endothelial markers and the acquisition of a mesenchymal phenotype. We hypothesized that keloid fibroblasts are of endothelial origin and that endothelial-to-mesenchymal transition substantially contributes to collagen accumulation during the development and progression of keloids. Wingless protein (Wnt-3a) protein expression was examined using immunohistochemistry in keloid tissues. Human dermal microvascular endothelial cells (HDMECs) were treated with Wnt-3a. mRNA and protein expression of endothelial (vascular endothelial cadherin) and mesenchymal (vimentin, snail family transcription factor [slug], and α-smooth muscle actin) cell markers were measured using real-time RT-PCR and immunocytochemistry, respectively. Additionally, coexpression of CD31 (cluster of differentiation 31), and endothelial cell marker, and vimentin in the vascular endothelium of keloid tissues was examined using immunofluorescence. Wnt-3a overexpression was observed in human keloid tissues. Wnt-3a treatment significantly reduced vascular endothelial cadherin mRNA expression and induced vimentin and slug mRNA expression in HDMECs. HDMECs became spindle-shaped and exhibited reduced expression of CD31 and increased expression of vimentin, slug, and α-smooth muscle actin. Moreover, coexpression of CD31 and vimentin was observed in the dermal vascular endothelium of keloid tissues from two patients with clinically active keloids. In conclusion, transient conversion of HDMECs to a mesenchymal phenotype may contribute to dermal fibrosis of keloid and hypertrophic scars.
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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
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
신정우(Shin, Jung U) ORCID logo https://orcid.org/0000-0001-5259-6879
양우익(Yang, Woo Ick) ORCID logo https://orcid.org/0000-0002-6084-5019
유대현(Lew, Dae Hyun)
이광훈(Lee, Kwang Hoon)
이원재(Lee, Won Jai) ORCID logo https://orcid.org/0000-0003-3056-0503
이주희(Lee, Ju Hee) ORCID logo https://orcid.org/0000-0002-1739-5956
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