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Rapamycin has been previously shown to inhibit EMT of PMCs and prevent peritoneal fibrosis. In this study, we investigated the undefined molecular mechanisms by which rapamycin inhibits EMT of PMCs. To define the protective effect of rapamycin, we initially used a rat PD model which was daily infused with 20 mL of 4.25% high glucose (HG) dialysis solution for 6 weeks to induce fibrosis. The HG rats showed decreased ultrafiltration volume and obvious fibroproliferative response, with markedly increased peritoneal thickness and higher expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) and transforming growth factor\u2010\u03b21. Rapamycin significantly ameliorated those pathological changes. Next, we treated rat PMCs with HG to induce EMT and\/or rapamycin for indicated time. Rapamycin significantly inhibited HG\u2010induced EMT, which manifests as increased expression of \u03b1\u2010SMA, fibronectin, and collagen I, decreased expression of E\u2010cadherin, and increased mobility. HG increased the phosphorylation of PI3K, Akt, and mTOR. Importantly, rapamycin inhibits the RhoA, Rac1, and Cdc42 activated by HG. Moreover, rapamycin repaired the pattern of F\u2010actin distribution induced by HG, reducing the formation of stress fiber, focal adhesion, lamellipodia, and filopodia. Thus, rapamycin shows an obvious protective effect on HG\u2010induced EMT, by inhibiting the activation of Rho GTPases (RhoA, Rac1, and Cdc42).<\/jats:p>","DOI":"10.1111\/febs.13740","type":"journal-article","created":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T20:27:52Z","timestamp":1461097672000},"page":"2309-2325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Rapamycin inhibits epithelial\u2010to\u2010mesenchymal transition of peritoneal mesothelium cells through regulation of Rho GTPases"],"prefix":"10.1111","volume":"283","author":[{"given":"Shilong","family":"Xiang","sequence":"first","affiliation":[{"name":"Kidney Disease Center The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Kidney Disease Center The First Affiliated Hospital 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