MiR-29a-3p inhibits fibrosis of diabetic kidney disease in diabetic mice <i>via</i> downregulation of DNA methyl transferase 3A and 3B
Ying Yang, Yi Chen, Jianying Tang, Jian Chen, Guiqing Li, Bing Feng, Jiao Mu
Abstract
BACKGROUND At present, the incidence of diabetic nephropathy is increasing year by year, and there are many studies on the pathogenesis of diabetic nephropathy, but it is still not completely clear. The final pathological result of diabetic nephropathy is mainly glomerular cell fibrosis, and the roles of micro-RNA (miRNA)-29 and DNA methyl transferase (DNMTs) in cell fibrosis have been confirmed in other studies, but there is a lack of relevant research in the kidney at present. AIM To study the potential involvement of miRNA-29a-3p in fibrosis related to diabetic kidney disease (DKD). METHODS The expression of miR-29a-3p, DNMT3A/3B, fibrosis-related molecules, Wnt3a, β-catenin, Janus kinase 2, and signal transducer and activator of transcription 3 was assessed in SV40MES13 cells and diabetic mice using quantitative real-time PCR and western blotting. Furthermore, the expression changes of fibrosis-related molecules were further analyzed using immunofluorescence and immunohistochemical blotting. The renal pathological changes of DKD in each group were also studied using hematoxylin-eosin and periodate-Schiff reaction staining. RESULTS In both the in vivo and in vitro experiments, it was observed that high glucose induction significantly decreased miR-29a-3p expression. As a result of this downregulation, DKD-related fibrosis was found to be promoted, as confirmed by elevated expression levels of α-smooth muscle actin, collagen type I, and fibronectin. MiR-29a-3p targets the 3’ non-coding regions of DNMT3A and DNMT3B and inhibits their expression. Inhibition of DNMT3A and DNMT3B can reverse the effect of miR-29a-3p downregulation on DKD-related fibrosis. CONCLUSION MiR-29a-3p can regulate Wnt/β-catenin and Janus kinase/signal transducer and activator of transcription signal pathways by regulating and inhibiting the expression of DNMT3A/3B and thus participate in the inhibition of DKD-related fibrosis.