Abstract
Abstract BACKGROUND AND AIMS Symmetric dimethylarginine (SDMA) is regarded as an independent cardiovascular risk factor in patients with chronic kidney diseases. Renal interstitial fibrosis is a common pathway of all kinds of chronic kidney diseases progressing to the end-stage of renal diseases. In this study, we investigated the role of SDMA in renal fibrosis and its underlining mechanisms. METHOD Normal saline (NS) and SDMA (2.50 µmol/kg) were administered to the kidney through the left ureter in a mouse model of unilateral ureteral obstruction (UUO). UUO kidneys were harvested on day 7. Western blotting and Masson's trichrome staining were performed to evaluate renal fibrosis. Moreover, human kidney 2 (HK2) cells were treated with various concentrations of SDMA (0.01 µM–10 µM) in the presence of 2.5 ng/mL TGF-β. Protein samples were collected from cells to measure the expression of fibrotic markers. RESULTS We observed that intrarenal administration of SDMA attenuated renal fibrosis as shown by Masson staining and Western blotting analysis of the expression of fibronectin, collagen-I and α smooth muscle actin (αSMA). In parallel, SDMA dose-dependently reduced the expression of pro-fibrotic proteins in TGF-β stimulated HK2 cells. Phosphorylation of Smad3 protein was analyzed in vivo and in vitro, which showed that SDMA inhibited phosphorylation of Smad3 in UUO kidneys and TGF-β stimulated HK2 cells. CONCLUSION Thus, our data suggest that renal SDMA exerts direct anti-fibrotic effects in fibrotic kidneys probably through inhibition of the Smad3 signalling pathway.
Published Version
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