MicroRNA-30下调可促进足状突细胞损伤并且可被糖皮质激素阻止

Downregulation of MicroRNA-30 facilitates podocyte injury and is prevented by glucocorticoids
作者:Wu, J. | Zheng, C. | Fan, Y. | Zeng, C. | Chen, Z. | Qin, W. | Zhang, C. | Zhang, W. | Wang, X. | Zhu, X. | Zhang, M. | Zen, K. | Liu, Z.
机构: 南京大学医学院 南京军区总医院肾病研究所
期刊: J AM SOC NEPHROL2014年1月1期25卷

Abstract

MicroRNAs (miRNAs) are essential for podocyte homeostasis, and the miR-30 family may be responsible for this action. However, the exact roles and clinical relevance of miR-30s remain unknown. In this study, we examined the expression of the miR-30 family in the podocytes of patients with FSGS and found that all members are downregulated. Treating cultured human podocytes with TGF-β, LPS, or puromycin aminonucleoside (PAN) also downregulated the miR-30 family. Podocyte cytoskeletal damage and apoptosis caused by treatment with TGF-β or PAN were ameliorated by exogenous miR-30 expression and aggravated by miR-30 knockdown. Moreover, we found that miR-30s exert their protective roles by direct inhibition of Notch1 and p53, which mediate podocyte injury. In rats, treatment with PAN substantially downregulated podocyte miR-30s and induced proteinuria and podocyte injury; however, transfer of exogenous miR-30a to podocytes of PAN-treated rats ameliorated proteinuria and podocyte injuryand reduced Notch1 activation. Finally, we demonstrated that glucocorticoid treatment maintains miR-30 expression in cultured podocytes treated with TGF-β, LPS, or PAN and in the podocytes of PAN-treated rats. Glucocorticoid-sustained miR-30 expression associated with reduced Notch1 activation and alleviated podocyte damage. Taken together, these findings demonstrate that miR-30s protect podocytes by targeting Notch1 and p53 and that the loss of miR-30s facilitates podocyte injury. In addition, sustained miR-30 expression may be a novel mechanism underlying the therapeutic effectiveness of glucocorticoids in treating podocytopathy.

通讯作者:Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, Jiangsu, China
学科代码:肾脏病学   关键词:MicroRNA-30
来源: Scopus
Scopus介绍:Scopus 于2004年11月正式推出,是目前全球规模最大的文摘和引文数据库。Scopus涵盖了由5000多家出版商出版发行的科技、医学和社会科学方面的18,000多种期刊,其中同行评审期刊16,500多种。相对于其他单一的文摘索引数据库而言,Scopus的内容更加全面,学科更加广泛,特别是在获取欧洲及亚太地区的文献方面,用户可检索出更多的文献数量。通过Scopus,用户可以检索到1823年以来的近4000万条摘要和题录信息,以及1996年以来所引用的参考文献。数据每日更新。 马上访问Scopus网站http://www.scopus.com/
顶一下(0
您可能感兴趣的文章
    发表评论网友评论(0)
      发表评论
      登录后方可发表评论,点击此处登录