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Reduced asymmetric dimethylarginine accumulation through inhibition of the type I protein arginine methyltransferases promotes renal fibrosis in obstructed kidneys 期刊论文

编号：

6785e1ff-d2ad-4356-976f-16a7f238a447
作者：

Wu, Ming(吴明)#*^[1]Lin, Pinglan#^[1]Li, Lin#^[2]Chen, Dongping(陈冬平)^[1]Yang, Xuejun^[1];Xu, Lin^[1];Zhou, Bing^[3];Wang, Chen(王琛)^[3]Zhang, Yuanyuan^[3];Luo, Cheng^[3];Ye, Chaoyang*^[1]
语种：

英文
期刊：

FASEB JOURNAL ISSN：0892-6638 2019 年 33 卷 6 期 (6948 - 6956) ; JUN
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关键词：

PRMT1 ADMA NO CKD
摘要：

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-beta. We found that treatment with PT1001B increased the deposition of extracellular matrix proteins, the expression of alpha smooth 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-beta-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.
推荐引用方式
GB/T 7714：

Wu Ming,Lin Pinglan,Li Lin, et al. Reduced asymmetric dimethylarginine accumulation through inhibition of the type I protein arginine methyltransferases promotes renal fibrosis in obstructed kidneys [J].FASEB JOURNAL,2019,33(6):6948-6956.
APA：

Wu Ming,Lin Pinglan,Li Lin,Chen Dongping,&Ye Chaoyang.(2019).Reduced asymmetric dimethylarginine accumulation through inhibition of the type I protein arginine methyltransferases promotes renal fibrosis in obstructed kidneys .FASEB JOURNAL,33(6):6948-6956.
MLA：

Wu Ming, et al. "Reduced asymmetric dimethylarginine accumulation through inhibition of the type I protein arginine methyltransferases promotes renal fibrosis in obstructed kidneys" .FASEB JOURNAL 33,6(2019):6948-6956.
入库时间：

1/6/2020 6:09:41 PM
更新时间：

1/6/2020 6:09:41 PM
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