Klotho mitigates cyclosporine A (CsA)-induced epithelial-mesenchymal transition (EMT) and renal fibrosis in rats

Klotho deficiency is implicated in various kidney diseases, including renal fibrosis. The aim of this study was to investigate the effect of Klotho administration on epithelial-mesenchymal transition (EMT) and renal fibrosis induced by cyclosporine A (CsA) in rats. CsA-induced renal fibrosis was established by oral administration of CsA (30 mg/kg) to rats on a low-salt diet for 28 days. Klotho was administered to rats by intraperitoneal injection. Renal pathological changes were evaluated by hematoxylin and eosin and Masson's trichrome staining. The EMT response was assessed by measuring the level of TGF-beta 1, E-cadherin and alpha-SMA by immunohistochemistry and Western blot. Administration of CsA for 28 days induced renal damage, decreased Klotho expression and activated the EMT response (demonstrated as increased TGF-beta 1 and alpha-SMA expression accompanied by decreased in E-cadherin expression). Treatment with Klotho significantly ameliorated pathological lesions of the kidney by modulating the expression of EMT-associated proteins in the kidney. Klotho inhibits CsA-induced EMT and renal fibrosis in rats. Klotho may serve as a therapeutic agent to minimize CsA-induced renal fibrosis.