Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPβ and histone H3
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
Jian Zhang
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Yan Li
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Jiaqi Liu
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Fu Han
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Jihong Shi
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Gaofeng Wu
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, P.R. China
Kejia Wang
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Kuo Shen
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Ming Zhao
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Xiaowen Gao
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Chenyang Tian
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
Yunchuan Wang
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China; Corresponding author
Ke Tao
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China; Corresponding author
Dahai Hu
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China; Corresponding author
Summary: 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.
