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.
Na Gao  1 Lulu Lu  1 Xiaolei Ma  1 Zhengyi Liu  1 Shuxia Yang  2 Gangwen Han  1
Affiliations
  • 1. Department of Dermatology, Peking University International Hospital, Beijing, China.
  • 2. Department of Dermatology and Venereology, National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital, Beijing, China.
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.
Products