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

文献类型：期刊论文

作者Wu, Ming1; Lin, Pinglan1; Li, Lin2; Chen, Dongping1; Yang, Xuejun1; Xu, Lin1; Zhou, Bing3; Wang, Chen3; Zhang, Yuanyuan3; Luo, Cheng3
刊名FASEB JOURNAL
出版日期2019-03-06
卷号33期号:6页码:6948-6956
关键词PRMT1 ADMA NO CKD
ISSN号0892-6638
DOI10.1096/fj.201802585RR
文献子类Article
英文摘要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.
WOS关键词RAT MODEL ; DISEASE ; PROGRESSION ; METABOLISM ; PATHWAYS
WOS研究方向Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
语种英语
WOS记录号WOS:000476114200022
出版者FEDERATION AMER SOC EXP BIOL
源URL[http://119.78.100.183/handle/2S10ELR8/309431]  
专题新药研究国家重点实验室
通讯作者Wu, Ming; Ye, Chaoyang
作者单位1.Shanghai Univ Tradit Chinese Med, Dept Nephrol, Shuguang Hosp,Shanghai Key Lab Tradit Chinese Cli, Key Lab Liver & Kidney Dis,Minist Educ,TCM,Inst K, Shanghai, Peoples R China;
2.Second Mil Med Univ, Shanghai Changzheng Hosp, Kidney Inst, Dept Nephrol, Shanghai, Peoples R China;
3.Chinese Acad Sci, Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai Inst Mat Med,State Key Lab Drug Res, Shanghai, Peoples R China
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.,Yang, Xuejun.,...&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.

入库方式： OAI收割

来源：上海药物研究所

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