Uv-induced reduction of acvr1c decreases srebp1 and acc expression by the suppression of smad2 phosphorylation in normal human epidermal keratinocytes

Yu Dan Tian, Min Hwa Chung, Qing Ling Quan, Dong Hun Lee, Eun Ju Kim, Jin Ho Chung

Research output: Contribution to journalArticlepeer-review

Abstract

Activin A receptor type 1C (ACVR1C), a type I transforming growth factor-β (TGF-β) re-ceptor, has been implicated in sensitive skin and psoriasis and is involved in the regulation of met-abolic homeostasis as well as cell proliferation and differentiation. In this study, we identified a novel role of ACVR1C in the ultraviolet (UV)-irradiation-induced reduction of epidermal lipogene-sis in human skin. UV irradiation decreased ACVR1C expression and epidermal triglyceride (TG) synthesis in human skin in vivo and in primary normal human epidermal keratinocytes (NHEK) in vitro. Lipogenic genes, including genes encoding acetyl-CoA carboxylase (ACC) and sterol regulatory element binding protein-1 (SREBP1), were significantly downregulated in UV-irradiated NHEK. ACVR1C knockdown by shRNA resulted in greater decreases in SREBP1 and ACC in response to UV irradiation. Conversely, the overexpression of ACVR1C attenuated the UV-induced decreases in SREBP1 and ACC. Further mechanistic study revealed that SMAD2 phosphorylation mediated the ACVR1C-induced lipogenic gene modulation. Taken together, a decrease in ACVR1C may cause UV-induced reductions in SREBP1 and ACC as well as epidermal TG synthesis via the suppression of SMAD2 phosphorylation. ACVR1C may be a target for preventing or treating UV-induced disruptions in lipid metabolism and associated skin disorders.

Original languageEnglish
Article number1101
Pages (from-to)1-10
Number of pages10
JournalInternational Journal of Molecular Sciences
Volume22
Issue number3
DOIs
StatePublished - 1 Feb 2021

Keywords

  • Acetyl CoA carboxylase
  • Activin A receptor type 1C
  • Epidermal lipogenesis
  • SMAD2 phosphorylation
  • Sterol regulatory element-binding protein-1
  • Ultraviolet

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