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Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPβ and histone H3
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. R...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9579505/ https://www.ncbi.nlm.nih.gov/pubmed/36274941 http://dx.doi.org/10.1016/j.isci.2022.105236 |
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author | Zhang, Jian Li, Yan Liu, Jiaqi Han, Fu Shi, Jihong Wu, Gaofeng Wang, Kejia Shen, Kuo Zhao, Ming Gao, Xiaowen Tian, Chenyang Wang, Yunchuan Tao, Ke Hu, Dahai |
author_facet | Zhang, Jian Li, Yan Liu, Jiaqi Han, Fu Shi, Jihong Wu, Gaofeng Wang, Kejia Shen, Kuo Zhao, Ming Gao, Xiaowen Tian, Chenyang Wang, Yunchuan Tao, Ke Hu, Dahai |
author_sort | Zhang, Jian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9579505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-95795052022-10-20 Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPβ and histone H3 Zhang, Jian Li, Yan Liu, Jiaqi Han, Fu Shi, Jihong Wu, Gaofeng Wang, Kejia Shen, Kuo Zhao, Ming Gao, Xiaowen Tian, Chenyang Wang, Yunchuan Tao, Ke Hu, Dahai iScience Article 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. Elsevier 2022-09-28 /pmc/articles/PMC9579505/ /pubmed/36274941 http://dx.doi.org/10.1016/j.isci.2022.105236 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Zhang, Jian Li, Yan Liu, Jiaqi Han, Fu Shi, Jihong Wu, Gaofeng Wang, Kejia Shen, Kuo Zhao, Ming Gao, Xiaowen Tian, Chenyang Wang, Yunchuan Tao, Ke Hu, Dahai Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPβ and histone H3 |
title | Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPβ and histone H3 |
title_full | Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPβ and histone H3 |
title_fullStr | Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPβ and histone H3 |
title_full_unstemmed | Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPβ and histone H3 |
title_short | Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPβ and histone H3 |
title_sort | adiponectin ameliorates hypertrophic scar by inhibiting yes-associated protein transcription through sirt1-mediated deacetylation of c/ebpβ and histone h3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9579505/ https://www.ncbi.nlm.nih.gov/pubmed/36274941 http://dx.doi.org/10.1016/j.isci.2022.105236 |
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