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

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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.

Original languageEnglish
Pages (from-to)435-442
Number of pages8
JournalWound Repair and Regeneration
Volume23
Issue number3
DOIs
Publication statusPublished - 2015 May 1

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All Science Journal Classification (ASJC) codes

  • Surgery
  • Dermatology

Cite this

Lee, W. J., Park, J. H., Shin, J. U., Noh, H., Lew, D. H., Yang, W. I., Yun, C. O., Lee, K. H., & Lee, J. H. (2015). Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis. Wound Repair and Regeneration, 23(3), 435-442. https://doi.org/10.1111/wrr.12300