Salvianolic acid B (SAB) can alleviate renal fibrosis and improve the renal function.To investigate the effect of SAB on renal tubulointerstitial fibrosis and explore its underlying mechanisms.Male...

The role of asymmetric dimethylarginine (ADMA) in chronic kidney disease (CKD) is unclear. Through inhibition of type I protein arginine methyltransferases (PRMTs), a novel strategy, we aimed to determine the effect of ADMA on renal fibrosis and explore its underlying working mechanisms. After sham or unilateral ureter ligation (UUO) operation, 20–25 g male c57 mice were treated with vehicle or PT1001B, an inhibitor of type I PRMTs, for 13 d. Moreover, human kidney 2 (HK2) and normal rat kidney 49F (NRK‐49F) cells were treated with various concentrations of PT1001B or ADMA in the presence of 2.5 ng/ml TGF‐β. We found that treatment with PT1001B increased the deposition of extracellular matrix proteins, the expression of αsmooth muscle actin, and connective tissue growth factor in UUO‐induced fibrotic kidneys, which is correlated with reduced expression of PRMT1, reduced the production of ADMA, and increased expression of uromodulin. In TGF‐β‐stimulated HK2 and NRK‐49F cells, PT1001B dose‐dependently inhibited ADMA production, increased NO concentrations, and enhanced the expression of profibrotic proteins. Exogenous addition of ADMA inhibited the expression of profibrotic proteins dose‐dependently and attenuated the profibrotic effect of PT1001B. Moreover, ADMA reduced the NO concentration in PT1001B‐treated HK2 cells. Finally, we conclude that ADMA has an antifibrotic effect in obstructed kidneys, and future application of type I PRMT inhibitor should be done cautiously for patients with CKD.—Wu, M., Lin, P., Li, L., Chen, D., Yang, X., Xu, L., Zhou, B., Wang, C., Zhang, Y., Luo, C., Ye, C. Reduced asymmetric dimethylarginine accumulation through inhibition of the type I protein arginine methyltransferases promotes renal fibrosis in obstructed kidneys. FASEB J. 33, 6948–6956 (2019). www.fasebj.org

Aims: To introduce our preliminary experience in using multislice computed tomographic (CT) angiography (MSCTA) to assess stenoses of the hemodialysis vascular access and to guide revising operation or percutaneous transluminal angioplasty (PTA). Methods: Contrast-enhanced 16-slice spiral CT was used to examine 22 hemodialysis patients with various dysfunctions of their vascular access. The transverse source images were reformatted as maximum intensity projection, volume-rendering, and multiple/curved planar reconstruction images. Results: The whole spectrum of arteriovenous fistulas (AVF) with the feeding artery, anastomoses, and outflow tract up to the superior caval vein was clearly displayed in all patients. According to the results of MSCTA, AVF-revising surgery was done in 11 patients, and PTA under the guide of digital subtraction angiography (DSA) was done in 5 patients. The results of MSCTA coincide with the findings of surgery or DSA in these 16 patients. Conclusions: In our opinion, MSCTA is a good noninvasive diagnostic technique to detect various hemodialysis vascular access abnormalities. It is more economical than DSA in the present medical settings and could replace DSA in the imaging of hemodialysis vascular access and provide important information for further AVF-revising surgery or PTA.

Background: Tanshinone I (Tan-I), an ingredient of Salvia miltiorrhiza, displays protective effects in several disease models. We aim to study the effect of Tan-I on renal fibrosis and explore its underlining mechanism. Methods: Rat renal fibroblasts (NRK-49F) were used as an in vitro model to study the effect of Tan-I. Mouse renal fibrosis model was induced by unilateral ureteral obstruction (UUO) or peritoneally injection of aristolochic acid I (AAI). Results: We found that Tan-I dose-dependently inhibited the expression of pro-fibrotic markers in rat renal fibroblasts. Masson staining and Western blotting analysis showed that Tan-I treatment attenuated renal fibrosis in UUO or AAI induced fibrotic kidneys. RNA sequencing analysis identified inhibin beta-A (INHBA), a ligand of TGF-β superfamily, as a downstream target of Tan-I in fibrotic kidneys, which were further verified by qPCR. Western blotting analysis showed that INHBA is up-regulated in UUO or AAI induced fibrotic kidneys and Tan-I reduced the expression of INHBA in fibrotic kidneys. Inhibition of INHBA by Tan-I was further confirmed in rat fibroblasts. Moreover, knockdown of INHBA reduced the expression of pro-fibrotic markers and abolished the ani-fibrotic effect of Tan-I in rat renal fibroblasts. Conclusions: We conclude that Tan-I attenuates fibrosis in fibrotic kidneys through inhibition of INHBA.