{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T07:06:53Z","timestamp":1793862413262,"version":"4.6.1"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"crossref","award":["2021A1515011482"],"award-info":[{"award-number":["2021A1515011482"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016799","name":"Natural Science Foundation of Guangzhou","doi-asserted-by":"crossref","award":["201904010255"],"award-info":[{"award-number":["201904010255"]}],"id":[{"id":"10.13039\/100016799","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82170693,81870465,81970623,81670646"],"award-info":[{"award-number":["82170693,81870465,81970623,81670646"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,8]]},"abstract":"<jats:p>\n                    Kidney fibrosis is the final common pathway of progressive kidney diseases, the underlying mechanisms of which are not fully understood. The purpose of the current study is to investigate a role of Piezo1, a mechanosensitive nonselective cation channel, in kidney fibrosis. In human fibrotic kidneys, Piezo1 protein expression was markedly upregulated. The abundance of Piezo1 protein in kidneys of mice with unilateral ureter obstruction (UUO) or with folic acid treatment was significantly increased. Inhibition of Piezo1 with nonspecific inhibitor GsMTx4 markedly ameliorated UUO- or folic acid\u2013induced kidney fibrosis. Mechanical stretch, compression, or stiffness induced Piezo1 activation and profibrotic responses in human HK2 cells and primary cultured mouse proximal tubular cells (mPTCs), which were greatly prevented by inhibition or silence of Piezo1. TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    induced increased Piezo1 expression and profibrotic phenotypic alterations in HK2 cells and mPTCs, which were again markedly prevented by inhibition of Piezo1. Activation of Piezo1 by Yoda1, a Piezo1 agonist, caused calcium influx and profibrotic responses in HK2 cells and induced calcium-dependent protease calpain2 activation, followed by adhesion complex protein talin1 cleavage and upregulation of integrin \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    . Also, Yoda1 promoted the link between ECM and integrin \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    . In conclusion, Piezo1 is involved in the progression of kidney fibrosis and profibrotic alterations in renal proximal tubular cells, likely through activating calcium\/calpain2\/integrin \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    pathway.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.152330","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T12:01:34Z","timestamp":1646136094000},"source":"Crossref","is-referenced-by-count":167,"title":["Mechanosensitive Piezo1 channels mediate renal fibrosis"],"prefix":"10.1172","volume":"7","author":[{"given":"Xiaoduo","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pathophysiology,"},{"name":"Institute of Hypertension, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglun","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology,"},{"name":"Institute of Hypertension, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baien","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology,"},{"name":"Institute of Hypertension, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhai","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-8643","authenticated-orcid":true,"given":"Nan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8229-2160","authenticated-orcid":true,"given":"Bin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2272-3851","authenticated-orcid":true,"given":"Jianding","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunling","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, and"},{"name":"Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2523-3145","authenticated-orcid":true,"given":"Weidong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology,"},{"name":"Institute of Hypertension, and"},{"name":"Department of Nephrology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2011.149"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00414.2012"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116995"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.002"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72269"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1159\/000446336"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.569322"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.04.018"},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2015.00082","article-title":"TGF-\u03b2\/Smad signaling in renal fibrosis","volume":"6","author":"Meng","year":"2015","journal-title":"Front Physiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2933-1"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.08.032"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201609037"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193270"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12088"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1578-z"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nature13701"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-016-1811-z"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87343"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2013.170"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2010.97"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07900716"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12073"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.10.5449"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.09.046"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1910650117"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.137273"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.02.026"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00036.2018"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00958"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180483"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00214.2019"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00123"},{"key":"B33","article-title":"Preparation of hydrogel substrates with tunable mechanical properties","volume":"Chapter 10","author":"Tse","year":"2010","journal-title":"Curr Protoc Cell Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.9b09337"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015050499"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2021.102367"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.03.163"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.121.17177"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-019-02167-3"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0234-9"},{"issue":"15","key":"B41","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1242\/jcs.190991","article-title":"Talin \u2014 the master of integrin adhesions","volume":"130","author":"Klapholz","year":"2017","journal-title":"J Cell Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.11.010"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.01.026"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0863-3"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020010009"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034227"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00576.2007"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1021\/bi200770q"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2006.09.030"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.528638"},{"key":"B51","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.07369","article-title":"Chemical activation of the mechanotransduction channel Piezo1","volume":"4","author":"Syeda","year":"2015","journal-title":"Elife"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00589.2014"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015080889"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05350.x"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091183"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00231.2016"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.2337\/db18-0090"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016080840"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/152330\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:21:03Z","timestamp":1779150063000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/152330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,8]]},"references-count":58,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4,8]]},"published-print":{"date-parts":[[2022,4,8]]}},"alternative-id":["10.1172\/jci.insight.152330"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.152330","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,8]]},"article-number":"e152330"}}