TAZ Reduces UVA-mediated Photoaging through Regulates Cell Proliferation in Skin Fibroblasts

Photochem Photobiol. 2023 Jan;99(1):153-159. doi: 10.1111/php.13654. Epub 2022 Jul 5.

Abstract

The transcriptional co-activator with PDZ-binding motif (TAZ) is a significant transcription factor downstream of the Hippo pathway regulating organ size, tissue regeneration, cell proliferation and apoptosis. Here, we report on TAZ in response to photoaging mediated by repeated UVA irradiation in skin fibroblasts. Continuous UVA irradiation caused a decrease in TAZ and targeted CTGF mRNA and protein expression in fibroblasts, accompanied by reduced cell proliferation, DNA damage, and cell cycle arrest in G1 phase and S phase reduction. Furthermore, P16 and P21 expression levels were increased, whereas Lamin B1 and Lamin A/C expression were decreased as a result of repeated UVA exposure. We further demonstrated that TAZ reduction enables photoaging caused by continuously UVA-irradiated fibroblasts. TAZ overexpression decreases G1 phase, augments the S phase and reduces P16 and P21 protein expression levels in fibroblasts. However, TAZ overexpressing cells exposed to chronic-UVA radiation show induced G1 phase arrest, an S phase reduction, and elevated P16 and P21 protein levels in fibroblasts, compared with TAZ overexpression cells. These findings suggest a novel function of TAZ to reduce photoaging in fibroblasts. This regulation implies that TAZ might be a viable therapeutic target for photoaging or UVA-related skin disorders.

MeSH terms

  • Cell Proliferation
  • Fibroblasts / radiation effects
  • Gene Expression Regulation
  • Humans
  • Skin / radiation effects
  • Skin Aging*
  • Skin Diseases*
  • Transcription Factors / metabolism
  • Ultraviolet Rays

Substances

  • Transcription Factors
  • WWTR1 protein, human