We investigated the protective effect of benidipine, by testing the changes of the activity of Rho kinase and transdifferentiation of renal tubular epithelium cells in vivo. Wistar rats were randomly divided into two groups: normal (N) and diabetes. STZ were used to make the rats type 1 diabetic and were randomly assigned as diabetes without treatment (D), diabetes treated with benidipine (B), and diabetes treated with fasudil (F) and treated for 3 months. Immunohistochemistry and western blotting were for protein expressions of ROCK1, -SMA, and E-cadherin and real-time PCR for the mRNA quantification of ROCK1. Compared with N group, D group had significant proliferation of glomerular mesangial matrix, increased cell number, thickened basement membrane, widely infiltrated by inflammatory cells and fibrosis in the renal interstitial, and dilated tubular. Those presentations in F and B groups were milder. Compared with N group, D group showed elevated MYPT1 phosphorylation, increased expression of ROCK1, -SMA protein, and ROCK1 mRNA and decreased expression of E-cadherin protein. B group showed attenuated MYPT1 phosphorylation, decreased ROCK1, -SMA protein, and ROCK1 mRNA expression and increased expression of E-cadherin protein. In conclusion, benidipine reduces the epithelium-mesenchymal transdifferentiation and renal interstitial fibrosis in diabetic kidney by inhibiting ROCK1 activity. 1. Introduction Benidipine is a triple calcium channel blocker, simultaneously blocking L, T, and N type channels. It is reported that the effect on T channel is stronger than that on L channel [1], making it a great potential protection for kidney. A number of studies explored the Rho signaling pathway, renal interstitial fibrosis, and tubular epithelium cell transdifferentiation (EMT) [2–4]. The blocking of T calcium channel (TCC) was reported to inhibit the activity of Rho kinase [5], and this is essential in podocyte effacement in immune complex-mediated glomerular disease and other kidney injuries [6]. Furthermore, under cellular stress, Rho kinase activation results in cytoskeletal rearrangement, stress fiber formation, and loss of cellular integrity and function [7]. Rho kinase inhibition prevented these changes and enhanced process formation [8]. These suggested that blocking T channel may have a protective effect on diabetic kidney and reduce epithelium-mesenchymal transdifferentiation and fibrosis via inhibiting ROCK1 (Rho kinase 1) activity. It was suggested that fasudil, a Rho kinase inhibitor, may attenuate EMT through reduced activation of RhoA/ROCK
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