Bronchial epithelial SIRT1 deficiency exacerbates cigarette smoke induced emphysema in mice through the FOXO3/PINK1 pathway
文献类型:期刊论文
作者 | Jiang, Hui1,2; Jiang, Yaona2,3; Xu, Yuanri2,3; Yuan, Dong2; Li, Yaqing4 |
刊名 | EXPERIMENTAL LUNG RESEARCH
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出版日期 | 2022-02-01 |
关键词 | COPD FOXO3 mitophagy PINK1 SIRT1 |
ISSN号 | 0190-2148 |
DOI | 10.1080/01902148.2022.2037169 |
通讯作者 | Li, Yaqing(lidoctor03@126.com) |
英文摘要 | Purpose: Cellular senescence and mitochondrial fragmentation are thought to be crucial components of the cigarette smoke(CS)-induced responses that contribute to the chronic obstructive pulmonary disease (COPD) development as a result of accelerated premature aging of the lung. Although there have been a few reports on the role of sirtuin 1(SIRT1) in mitochondrial homeostasis, senescence and inflammation, whether SIRT1/FOXO3/PINK1 signaling mediated mitophagy ameliorates cellular senescence in COPD is still unclear. This study aimed to ascertain whether SIRT1 regulates cellular senescence via FOXO3/PINK1-mediated mitophagy in COPD. Methods: To investigate the effect of CS exposure and SIRT1 deficiency on mitophagy and senescence in the lung, a SIRT1 knockout(KO) mouse model was used. Airway resistance, cellular senescence mitochondrial injury, mitophagy, cellular architecture and protein expression levels in lung tissues, from SIRT1 KO and wild-type(WT) COPD model mice exposed to CS for 6 months were examined by western blotting, histochemistry, immunofluorescence and transmission electron microscopy(TEM). Results: In CS exposed mice, SIRT1 deficiency exacerbated airway resistance and cellular senescence, increased FOXO3 acetylation and decreased PINK1 protein levels and attenuated mitophagy. Mechanistically, the damaging effect of SIRT1 deficiency on lung tissue was attributed to increased FOXO3 acetylation and decreased PINK1 levels, and attenuated mitophagy. In vitro, mitochondrial damage and cellular sensitivity in response to CS exposure were more severe in control cells than in cells treated with aSIRT1 activator. SIRT1 activation SIRT1 activation decreased FOXO3 acetylation and increased the protein levels of PINK1 and enhanced mitophagy. Conclusion: These results demonstrated that the detrimental effects of SIRT1 deficiency on cell senescence associated with insufficient mitophagy, and involved the FOXO3/PINK1 signaling pathway. |
WOS关键词 | OXIDATIVE STRESS ; CELL SENESCENCE ; MITOPHAGY ; AUTOPHAGY ; FRAGMENTATION ; PROTECTS ; PINK1 |
资助项目 | National Natural Science Foundation of China[8187010048] |
WOS研究方向 | Respiratory System |
语种 | 英语 |
WOS记录号 | WOS:000753910100001 |
出版者 | TAYLOR & FRANCIS INC |
资助机构 | National Natural Science Foundation of China |
源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/127500] ![]() |
专题 | 中国科学院合肥物质科学研究院 |
通讯作者 | Li, Yaqing |
作者单位 | 1.Soochow Univ, Dept Clin Med, Med Coll, Suzhou, Jiangsu, Peoples R China 2.Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Dept Internal Med, Peoples Hosp, Hangzhou, Zhejiang, Peoples R China 3.Zhejiang Chinese Med Univ, Grad Dept, Hangzhou, Zhejiang, Peoples R China 4.Univ Chinese Acad Sci, Dept Internal Med, Zhejiang Canc Hosp, Canc Hosp, Hangzhou, Zhejiang, Peoples R China |
推荐引用方式 GB/T 7714 | Jiang, Hui,Jiang, Yaona,Xu, Yuanri,et al. Bronchial epithelial SIRT1 deficiency exacerbates cigarette smoke induced emphysema in mice through the FOXO3/PINK1 pathway[J]. EXPERIMENTAL LUNG RESEARCH,2022. |
APA | Jiang, Hui,Jiang, Yaona,Xu, Yuanri,Yuan, Dong,&Li, Yaqing.(2022).Bronchial epithelial SIRT1 deficiency exacerbates cigarette smoke induced emphysema in mice through the FOXO3/PINK1 pathway.EXPERIMENTAL LUNG RESEARCH. |
MLA | Jiang, Hui,et al."Bronchial epithelial SIRT1 deficiency exacerbates cigarette smoke induced emphysema in mice through the FOXO3/PINK1 pathway".EXPERIMENTAL LUNG RESEARCH (2022). |
入库方式: OAI收割
来源:合肥物质科学研究院
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