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.

Involvement of miR‐27a‐3p in diabetic nephropathy via affecting renal fibrosis, mitochondrial dysfunction, and endoplasmic reticulum stress

“…In the present study, we showed that (Conserva et al, 2019). MiR-379-5p could alleviate renal fibrosis by targeting LIN28B in the in vivo and in vitro models of DN (Li, Wang, Xu, Liu, & Yu, 2019). Sun et al (2020) indicated that miR-544 relieves DN via inhibiting renal fibrosis and inflammatory response by targeting has been found to be upregulated in type 2 diabetic patients compared with nondiabetic individuals (Dahlmans et al, 2017).…”

Knock-Down of Long Non-Coding RNA ANRIL Suppresses Mouse Mesangial Cell Proliferation, Fibrosis, Inflammation via Regulating Wnt/β-Catenin and MEK/ERK Pathways in Diabetic Nephropathy

“…During the progression of diabetes, there are multiple pathological characteristics that sign the development of DN. To begin with, glomerular hypertrophy is caused by the accumulation of ECM, the upregulation of VGEF, as well as the proliferation of glomerular mesangial cells, and leads to glomerular hyper perfusion [17]. Besides, interstitial fibrosis is a gross indicator that includes accumulation or remodeling fibronectin, laminin and collagen, which substantially leads to the scarring of glomeruli in the kidney and reduces glomerular filtration rate [1].…”

Psoralen alleviates high glucose-induced HK-2 cell injury by inhibition of Smad 2 signaling via upregulation of microRNA 874

“…Since miR-214, miR-379-5p, miR-874, miR-770-5p and miR-22 have been reported to involve in the pathogenesis of DN [20,[23][24][25][26], RT-qPCR was performed to explore the interaction of psoralen and these miRNAs. The result indicated that the expression of miR-874 was significantly upregulated by psoralen in HK-2 cells (Fig.…”