MicroRNA?379?5p suppresses renal fibrosis by regulating the LIN28/let?7 axis in diabetic nephropathy.

ABSTRACT: MicroRNAs (miRNAs or miRs) play an important role in pathological processes in diabetic nephropathy (DN). This study aimed to explore whether miR?379?5p is associated with renal fibrosis in DN and to elucidate the underlying mechanisms. In vitro experiments indicated that miR?379?5p expression was downregulated by high glucose (HG) treatment in mouse mesangial cells (MMCs). Transfection with miR?379?5p mimics suppressed the proliferation and the accumulation of extracellular matrix (ECM) components, which were promoted by HG treatment. LIN28B was proven to be a direct target of miR?379?5p by luciferase report assay. In addition, the loss of expression of LIN28B, as well as the decrease in cell proliferation and in the accumulation of ECM components, which were induced by the knockdown of LIN28B, were attenuated in the MMCs following transfection with miR?379?5p inhibitors. Furthermore, type 2 diabetic db/db mice were used to examine the efficiency of miR?379?5p agomir in the alleviation of renal fibrosis. Consistent with the results of the in vitro experiments, miR?379?5p agomir suppressed mesangial cell proliferation and the accumulation of ECM components by regulating the LIN28B/let?7 pathway. Taken together, the findings of this study suggest that miR?379?5p is highly involved in renal fibrosis in DN, and that it may be a potential effective therapeutic target for DN.

SUBMITTER: Li N 

PROVIDER: S-EPMC6777678 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature