{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:00:16Z","timestamp":1784761216948,"version":"3.55.0"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Kidney Blood Press Res"],"abstract":"<jats:p>Introduction: Hyperglycaemia induces the production of a large quantity of reactive oxygen species (ROS) and activates the transforming growth factor \u03b21(TGF-\u03b21)\/Smad signalling pathway, which is the main initiating factor in the formation of diabetic nephropathy. Indoxyl sulfate (IS) is a protein-binding gut-derived uraemic toxin that localizes to podocytes, induces oxidative stress and inflames podocytes. The involvement of podocyte damage in diabetic nephropathy through the TGF-\u03b21\/) signalling pathway is still unclear. Methods: In this study, we cultured differentiated rat podocytes in vitro and measured the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a and \u03b1-SMA by quantitative real-time PCR (qRT\u2012PCR) and western blotting after siRNA-mediated TGF-\u03b21 silencing, TGF-\u03b21 overexpression and the presence of the ROS inhibitor acetylcysteine. We detected the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a, SRGAP2a in the Smad2\/3, phosphorylated-Smad2\/3 (p-Smad2\/3), Smad7, NADPH oxidase 4 (NOX4), and ROS levels under high glucose (HG) and IS conditions. Results: The results indicated that nephrin, synaptopodin, CD2AP and SRGAP2a expressions were significantly upregulated and \u03b1-SMA expression was significantly downregulated in the presence of HG under siRNA-mediated TGF-\u03b21 silencing or after the addition of acetylcysteine. However, in the presence of HG, the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a were significantly downregulated, and the expression of \u03b1-SMA was significantly upregulated with the overexpression of TGF-\u03b21. IS supplementation under HG conditions further significantly reduced the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a; altered the expressions of Smad2\/3, p-Smad2\/3, Smad7 and NOX4; and increased ROS production in podocytes. Conclusions: This study suggests that IS may modulate the expression of nephrin, synaptopodin, CD2AP and SRGAP2a by regulating the ROS and TGF-\u03b21\/Smad signalling pathways, providing new theoretical support for the treatment of diabetic nephropathy.<\/jats:p>","DOI":"10.1159\/000538858","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T01:37:08Z","timestamp":1715391428000},"source":"Crossref","is-referenced-by-count":9,"title":["Indoxyl sulfate aggravates podocyte damage through the TGF-\u03b21\/Smad\/ROS signaling pathway"],"prefix":"10.1159","author":[{"given":"Miao","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Xun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghua","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2024,5,10]]},"container-title":["Kidney and Blood Pressure Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/kbr\/article-pdf\/doi\/10.1159\/000538858\/4227722\/000538858.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/kbr\/article-pdf\/doi\/10.1159\/000538858\/4227722\/000538858.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:16:36Z","timestamp":1745421396000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000538858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,10]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000538858","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.25780419","asserted-by":"subject"}]},"ISSN":["1420-4096","1423-0143"],"issn-type":[{"value":"1420-4096","type":"print"},{"value":"1423-0143","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,10]]}}}