Adiponectin Ameliorates Hypertrophic Scar by Inhibiting Yes-associated Protein Transcription Through SIRT1-mediated Deacetylation of C/EBPβ and Histone H3

Overview

Journal iScience

Publisher Cell Press

Date 2022 Oct 24

PMID 36274941

Authors

Jian Zhang

Yan Li

Jiaqi Liu

Fu Han

Jihong Shi

Gaofeng Wu

Kejia Wang

Kuo Shen

Ming Zhao

Xiaowen Gao

Chenyang Tian

Yunchuan Wang

Ke Tao

Dahai Hu

Affiliations

Soon will be listed here.

Abstract

The clinical correlation between adiponectin (APN) signal and hypertrophic scar (HS) remains unclear. Here, we found significantly reduced expression of APN receptors (AdipoR1/2) in HS tissues and derived fibroblasts (HFs), suggesting that HS formation may be associated with APN/AdipoR1/2 decline. RNA sequencing and RT-PCR validation revealed that APN significantly elevated the expression of . Both and experiments confirmed that SIRT1 plays important role in APN inhibiting the fibrotic phenotype transformation and proliferation of scar fibroblasts and improving skin fibrosis. Mechanistically, SIRT1 inhibited the acetylation of C/EBPβ K39, histone H3K27, and H3K9, resulting in impaired transcription activity of C/EBPβ and compact chromatin conformation, thus preventing C/EBPβ from activating the transcription of . Moreover, we found that YAP was critical for the transcriptional regulation of , and by TEAD4. In conclusion, our study revealed the role of APN in antagonizing HS fibrosis by regulating the SIRT1/C/EBPβ/YAP pathway.

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