Extracellular HSP90α promotes cellular senescence by modulating TGF‐β signaling in pulmonary fibrosis
Recent findings suggest that extracellular heat shock protein 90α (eHSP90α) promotes pulmonary fibrosis, but the underlying mechanisms are not well understood. Aging, especially cellular senescence, is a critical risk factor for idiopathic pulmonary fibrosis (IPF). Here, we aim to investigate the ro...
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| Veröffentlicht in: | The FASEB journal 2022-08, Vol.36 (8), p.e22475-n/a |
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| creator | Zhong, Wenshan Chen, Weimou Liu, Yuanyuan Zhang, Jinming Lu, Ye Wan, Xuan Qiao, Yujie Huang, Haohua Zeng, Zhaojin Li, Wei Meng, Xiaojing Zhao, Haijin Zou, Mengchen Cai, Shaoxi Dong, Hangming |
| description | Recent findings suggest that extracellular heat shock protein 90α (eHSP90α) promotes pulmonary fibrosis, but the underlying mechanisms are not well understood. Aging, especially cellular senescence, is a critical risk factor for idiopathic pulmonary fibrosis (IPF). Here, we aim to investigate the role of eHSP90α on cellular senescence in IPF. Our results found that eHSP90α was upregulated in bleomycin (BLM)‐induced mice, which correlated with the expression of senescence markers. This increase in eHSP90α mediated fibroblast senescence and facilitated mitochondrial dysfunction. eHSP90α activated TGF‐β signaling through the phosphorylation of the SMAD complex. The SMAD complex binding to p53 and p21 promoters triggered their transcription. In vivo, the blockade of eHSP90α with 1G6‐D7, a specific eHSP90α antibody, in old mice attenuated the BLM‐induced lung fibrosis. Our findings elucidate a crucial mechanism underlying eHSP90α‐induced cellular senescence, providing a framework for aging‐related fibrosis interventions. |
| doi_str_mv | 10.1096/fj.202200406RR |
| format | Article |
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Aging, especially cellular senescence, is a critical risk factor for idiopathic pulmonary fibrosis (IPF). Here, we aim to investigate the role of eHSP90α on cellular senescence in IPF. Our results found that eHSP90α was upregulated in bleomycin (BLM)‐induced mice, which correlated with the expression of senescence markers. This increase in eHSP90α mediated fibroblast senescence and facilitated mitochondrial dysfunction. eHSP90α activated TGF‐β signaling through the phosphorylation of the SMAD complex. The SMAD complex binding to p53 and p21 promoters triggered their transcription. In vivo, the blockade of eHSP90α with 1G6‐D7, a specific eHSP90α antibody, in old mice attenuated the BLM‐induced lung fibrosis. Our findings elucidate a crucial mechanism underlying eHSP90α‐induced cellular senescence, providing a framework for aging‐related fibrosis interventions.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.202200406RR</identifier><language>eng</language><subject>cellular senescence ; HSP90 heat‐shock proteins ; mitochondria ; pulmonary fibrosis ; reactive oxygen species ; transforming growth factor beta</subject><ispartof>The FASEB journal, 2022-08, Vol.36 (8), p.e22475-n/a</ispartof><rights>2022 The Authors. published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3585-aaf28b7e81b1d683116519430c5cd9f9c77dfb608eabb1aa3e32184dc46aaf053</citedby><cites>FETCH-LOGICAL-c3585-aaf28b7e81b1d683116519430c5cd9f9c77dfb608eabb1aa3e32184dc46aaf053</cites><orcidid>0000-0003-2816-8262 ; 0000-0002-4476-9829</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.202200406RR$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.202200406RR$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Zhong, Wenshan</creatorcontrib><creatorcontrib>Chen, Weimou</creatorcontrib><creatorcontrib>Liu, Yuanyuan</creatorcontrib><creatorcontrib>Zhang, Jinming</creatorcontrib><creatorcontrib>Lu, Ye</creatorcontrib><creatorcontrib>Wan, Xuan</creatorcontrib><creatorcontrib>Qiao, Yujie</creatorcontrib><creatorcontrib>Huang, Haohua</creatorcontrib><creatorcontrib>Zeng, Zhaojin</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Meng, Xiaojing</creatorcontrib><creatorcontrib>Zhao, Haijin</creatorcontrib><creatorcontrib>Zou, Mengchen</creatorcontrib><creatorcontrib>Cai, Shaoxi</creatorcontrib><creatorcontrib>Dong, Hangming</creatorcontrib><title>Extracellular HSP90α promotes cellular senescence by modulating TGF‐β signaling in pulmonary fibrosis</title><title>The FASEB journal</title><description>Recent findings suggest that extracellular heat shock protein 90α (eHSP90α) promotes pulmonary fibrosis, but the underlying mechanisms are not well understood. Aging, especially cellular senescence, is a critical risk factor for idiopathic pulmonary fibrosis (IPF). Here, we aim to investigate the role of eHSP90α on cellular senescence in IPF. Our results found that eHSP90α was upregulated in bleomycin (BLM)‐induced mice, which correlated with the expression of senescence markers. This increase in eHSP90α mediated fibroblast senescence and facilitated mitochondrial dysfunction. eHSP90α activated TGF‐β signaling through the phosphorylation of the SMAD complex. The SMAD complex binding to p53 and p21 promoters triggered their transcription. In vivo, the blockade of eHSP90α with 1G6‐D7, a specific eHSP90α antibody, in old mice attenuated the BLM‐induced lung fibrosis. Our findings elucidate a crucial mechanism underlying eHSP90α‐induced cellular senescence, providing a framework for aging‐related fibrosis interventions.</description><subject>cellular senescence</subject><subject>HSP90 heat‐shock proteins</subject><subject>mitochondria</subject><subject>pulmonary fibrosis</subject><subject>reactive oxygen species</subject><subject>transforming growth factor beta</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNqFUM1KAzEYDKJgrV495-hl65dkk02OWmwrFJS2nkM2my0p-1M3W7Q3H8FX0QfpQ_gkbqmIN08fzDczzAxClwQGBJS4zlcDCpQCxCBmsyPUI5xBJKSAY9QDqWgkBJOn6CyEFQAQIKKH_N1r2xjrimJTmAZP5o8Kdh943dRl3bqAfz_BVS5YV1mH0y0u66xDW18t8WI8-np7333i4JeVKfaQr_B6U5R1ZZotzn3a1MGHc3SSmyK4i5_bR0-ju8VwEk0fxvfDm2lkGZc8MianMk2cJCnJhGSECE5UzMBym6lc2STJ8lSAdCZNiTHMMUpknNlYdFLgrI-uDr5dh-eNC60ufdjXMJWrN0FToQSAAsY66uBAtV3C0LhcrxtfdqE1Ab3fVOcr_WfTTsAPghdfuO0_bD2a31JK44Szb9SXfeE</recordid><startdate>202208</startdate><enddate>202208</enddate><creator>Zhong, Wenshan</creator><creator>Chen, Weimou</creator><creator>Liu, Yuanyuan</creator><creator>Zhang, Jinming</creator><creator>Lu, Ye</creator><creator>Wan, Xuan</creator><creator>Qiao, Yujie</creator><creator>Huang, Haohua</creator><creator>Zeng, Zhaojin</creator><creator>Li, Wei</creator><creator>Meng, Xiaojing</creator><creator>Zhao, Haijin</creator><creator>Zou, Mengchen</creator><creator>Cai, Shaoxi</creator><creator>Dong, Hangming</creator><scope>24P</scope><scope>WIN</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2816-8262</orcidid><orcidid>https://orcid.org/0000-0002-4476-9829</orcidid></search><sort><creationdate>202208</creationdate><title>Extracellular HSP90α promotes cellular senescence by modulating TGF‐β signaling in pulmonary fibrosis</title><author>Zhong, Wenshan ; Chen, Weimou ; Liu, Yuanyuan ; Zhang, Jinming ; Lu, Ye ; Wan, Xuan ; Qiao, Yujie ; Huang, Haohua ; Zeng, Zhaojin ; Li, Wei ; Meng, Xiaojing ; Zhao, Haijin ; Zou, Mengchen ; Cai, Shaoxi ; Dong, Hangming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3585-aaf28b7e81b1d683116519430c5cd9f9c77dfb608eabb1aa3e32184dc46aaf053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>cellular senescence</topic><topic>HSP90 heat‐shock proteins</topic><topic>mitochondria</topic><topic>pulmonary fibrosis</topic><topic>reactive oxygen species</topic><topic>transforming growth factor beta</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhong, Wenshan</creatorcontrib><creatorcontrib>Chen, Weimou</creatorcontrib><creatorcontrib>Liu, Yuanyuan</creatorcontrib><creatorcontrib>Zhang, Jinming</creatorcontrib><creatorcontrib>Lu, Ye</creatorcontrib><creatorcontrib>Wan, Xuan</creatorcontrib><creatorcontrib>Qiao, Yujie</creatorcontrib><creatorcontrib>Huang, Haohua</creatorcontrib><creatorcontrib>Zeng, Zhaojin</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Meng, Xiaojing</creatorcontrib><creatorcontrib>Zhao, Haijin</creatorcontrib><creatorcontrib>Zou, Mengchen</creatorcontrib><creatorcontrib>Cai, Shaoxi</creatorcontrib><creatorcontrib>Dong, Hangming</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhong, Wenshan</au><au>Chen, Weimou</au><au>Liu, Yuanyuan</au><au>Zhang, Jinming</au><au>Lu, Ye</au><au>Wan, Xuan</au><au>Qiao, Yujie</au><au>Huang, Haohua</au><au>Zeng, Zhaojin</au><au>Li, Wei</au><au>Meng, Xiaojing</au><au>Zhao, Haijin</au><au>Zou, Mengchen</au><au>Cai, Shaoxi</au><au>Dong, Hangming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extracellular HSP90α promotes cellular senescence by modulating TGF‐β signaling in pulmonary fibrosis</atitle><jtitle>The FASEB journal</jtitle><date>2022-08</date><risdate>2022</risdate><volume>36</volume><issue>8</issue><spage>e22475</spage><epage>n/a</epage><pages>e22475-n/a</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Recent findings suggest that extracellular heat shock protein 90α (eHSP90α) promotes pulmonary fibrosis, but the underlying mechanisms are not well understood. Aging, especially cellular senescence, is a critical risk factor for idiopathic pulmonary fibrosis (IPF). Here, we aim to investigate the role of eHSP90α on cellular senescence in IPF. Our results found that eHSP90α was upregulated in bleomycin (BLM)‐induced mice, which correlated with the expression of senescence markers. This increase in eHSP90α mediated fibroblast senescence and facilitated mitochondrial dysfunction. eHSP90α activated TGF‐β signaling through the phosphorylation of the SMAD complex. The SMAD complex binding to p53 and p21 promoters triggered their transcription. In vivo, the blockade of eHSP90α with 1G6‐D7, a specific eHSP90α antibody, in old mice attenuated the BLM‐induced lung fibrosis. 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| subjects | cellular senescence HSP90 heat‐shock proteins mitochondria pulmonary fibrosis reactive oxygen species transforming growth factor beta |
| title | Extracellular HSP90α promotes cellular senescence by modulating TGF‐β signaling in pulmonary fibrosis |
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