{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:53:54Z","timestamp":1792029234775,"version":"4.4.0"},"reference-count":59,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T00:00:00Z","timestamp":1532304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Membrane rafts (MRs)\u2013redox signalling pathway is activated in response to transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) stimulation in renal tubular cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This pathway contributes to TGF\u20101\u03b2\u2010induced epithelial\u2013mesenchymal transition (EMT) in renal tubular cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The the MRs\u2013redox signalling pathway is activated in renal tubular cells isolated from angiotensin II (AngII)\u2010induced hypertensive rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of this pathway attenuated renal inflammation and fibrosis in AngII\u2010induced hypertension.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The membrane rafts (MRs)\u2013redox pathway is characterized by NADPH oxidase subunit clustering and activation through lysosome fusion, V\u2010type proton ATPase subunit E2 (encoded by the Atp6v1e2 gene) translocation and sphingomyelin phosphodiesterase 1 (SMPD1, encoded by the SMPD1 gene) activation. In the present study, we hypothesized that the MRs\u2013redox\u2010derived reactive oxygen species (ROS) are involved in renal inflammation and fibrosis by promoting renal tubular epithelial\u2013mesenchymal transition (EMT). Results show that transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) acutely induced MR formation and ROS production in NRK\u201052E cells, a rat renal tubular cell line. In addition, transfection of Atp6v1e2 small hairpin RNAs (shRNA) and SMPD1 shRNA attenuated TGF\u2010\u03b21\u2010induced changes in EMT markers, including E\u2010cadherin, \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) and fibroblast\u2010specific protein\u20101 (FSP\u20101) in NRK\u201052E cells. Moreover, Erk1\/2 activation may be a downstream regulator of the MRs\u2013redox\u2010derived ROS, because both shRNAs significantly inhibited TGF\u2010\u03b21\u2010induced Erk1\/2 phosphorylation. Further <jats:italic>in vivo<\/jats:italic> study shows that the renal tubular the MRs\u2013redox signalling pathway was activated in angiotensin II (AngII)\u2010induced hypertension, as indicated by the increased NADPH oxidase subunit Nox4 fraction in the MR domain, SMPD1 activation and increased ROS content in isolated renal tubular cells. Finally, renal transfection of Atp6v1e2 shRNA and SMPD1 shRNA significantly prevented renal fibrosis and inflammation, as indicated by the decrease of \u03b1\u2010SMA, fibronectin, collagen I, monocyte chemoattractant protein\u20101 (MCP\u20101), intercellular cell adhesion molecule\u20101 (ICAM\u20101) and tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) in kidneys from AngII\u2010infused rats. It was concluded that the the MRs\u2013redox signalling pathway is involved in TGF\u2010\u03b21\u2010induced renal tubular EMT and renal inflammation\/fibrosis in AngII\u2010induced hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp275952","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T15:11:52Z","timestamp":1528125112000},"page":"3603-3616","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Membrane rafts\u2013redox signalling pathway contributes to renal fibrosis via modulation of the renal tubular epithelial\u2013mesenchymal transition"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9702-0523","authenticated-orcid":false,"given":"Wei\u2010Qing","family":"Han","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Hypertension, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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