title: Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis.
abstract: 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.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Jai
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji Hun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jung U
authors.initials: JU
authors.lastname: Shin
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Noh
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Lew
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Woo Ick
authors.initials: WI
authors.lastname: Yang
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.
authors.forename: Chae Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kwang Hoon
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000473:pathology*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007627:Keloid / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D060509:Wnt3A Protein / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D042461:Vascular Endothelial Growth Factor A; D060509:Wnt3A Protein