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
SIRT1. Both in vitro and in vivo 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 YAP. Moreover, we found that YAP was critical for the transcriptional regulation of CTGF, CCND1, and CCNE1 by TEAD4. In conclusion, our study revealed the role of APN in antagonizing HS
fibrosis by regulating the
SIRT1/C/EBPβ/YAP pathway.