biostudies-literatureZhao XNatural Science Foundation of Guangdong Provincethe National Natural Science Foundation of ChinaNatural Science Foundation of Guangzhoue152330https://www.ebi.ac.uk/biostudies/studies/S-EPMC9057604biostudies-literatureUnknown7(7)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-induced 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), wJCI insightMechanosensitive Piezo1 channels mediate renal fibrosis.PMC90576042019040102552021A151501148282170693,81870465,81970623,81670646Zhou NLi JLi CJiang BLin YWang WKong YXu JZhao XLiang BCheng JfalseMechanosensitive Piezo1 channels mediate renal fibrosis.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-induced 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), w2022-01-01T00:00:00Z2022 Apr2025-04-05T13:23:40.157Z2025-04-05T13:23:40.157ZS-EPMC90576043523097910.1172/jci.insight.152330