Research Paper Volume 11, Issue 10 pp 3055—3079
MiR-320a induces diabetic nephropathy via inhibiting MafB
- 1 , 430030, Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
received: October 30, 2018 ; accepted: May 6, 2019 ; published: May 17, 2019 ;https://doi.org/10.18632/aging.101962
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Copyright: He et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Multiple studies indicate that microRNAs (miRNAs) are involved in diabetes. However, the roles of miRNA in the target organ damages in diabetes remain unclear. This study investigated the functions of miR-320a in diabetic nephropathy (DN). In this study, db/db mice were used to observe the changes in podocytes and their function in vivo, as well as in cultured mouse podocyte cells (MPC5) exposed to high glucose in vitro. To further explore the role of miR-320a in DN, recombinant adeno-associated viral particle was administered intravenously to manipulate the expression of miR-320a in db/db mice. Overexpression of miR-320a markedly promoted podocyte loss and dysfunction in DN, including mesangial expansion and increased levels of proteinuria, serum creatinine and urea nitrogen. Furthermore, MafB was identified as a direct target of miR-320a through AGO2 co-immunoprecipitation, luciferase reporter assay, and Western blotting. Moreover, re-expression of MafB rescued miR-320a-induced podocyte loss and dysfunction by upregulating the expressions of Nephrin and glutathione peroxidase 3 (Gpx3). Our data indicated that miR-320a aggravated renal disfunction in DN by targeting MafB and downregulating Nephrin and Gpx3 in podocytes, which suggested that miR-320a could be a potential therapeutic target of diabetic nephropathy.