Targeted inhibition of YAP/TAZ alters the biological behaviours of keloid fibroblasts

Exp Dermatol. 2022 Mar;31(3):320-329. doi: 10.1111/exd.14466. Epub 2021 Oct 19.

Abstract

Abnormal activation of fibroblasts plays a crucial role in keloid development. However, the mechanism of fibroblast activation remains to be determined. YAP/TAZ are key molecules in the Hippo signalling pathway that promote cell proliferation and inhibit apoptosis. Here, we show that keloid fibroblasts have higher levels of YAP/TAZ mRNA and proteins on primary culture. Targeted knockdown of endogenous YAP or TAZ significantly inhibited cell proliferation, reduced cell migration, induced cell apoptosis and down-regulated collagen1a1 production by keloid fibroblasts. Moreover, we demonstrate that verteporfin, an inhibitor of YAP/TAZ, has similar but stronger inhibitory effects on fibroblasts compared to YAP/TAZ knockdown. Our study provides evidence that YAP/TAZ may be involved in the pathogenesis of keloids. Targeted inhibition of YAP/TAZ could change the biological behaviours of fibroblasts and can potentially be used as therapy for keloids.

Keywords: YAP/TAZ; fibroblasts; keloid; verteporfin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fibroblasts / metabolism
  • Humans
  • Keloid* / metabolism
  • Transcription Factors / genetics
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Verteporfin / metabolism
  • Verteporfin / pharmacology

Substances

  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Verteporfin