Overexpression of mm9_circ_013935 alleviates renal inflammation and fibrosis in diabetic nephropathy via the miR-153-3p/NFIC axis.

Abstract

Circ-RBM4 (mm9_circ_013935) has been revealed to have low expression in the renal tissues of diabetic nephropathy (DN) mice, and its underlying regulatory mechanism remains unexplored. The high glucose (HG) - treated mouse podocytes were used to establish DN cell models. A cell counting kit-8 assay was used to examine the viability of mouse podocytes. The expression of proteins related to fibrosis (collagen I, collagen III, fibronectin) was detected using Western blot. The concentration of inflammation cytokines (tumor necrosis factor α, interleukin 1β (IL-1β), IL-8) in mouse podocytes was assessed by ELISA. The interaction between genes was explored by luciferase reporter assays. HG treatment decreased the viability and elevated the expression of fibrosis and inflammation factors in mouse podocytes. Circ-RBM4 expression was downregulated in HG-treated mouse podocytes. Circ-RBM4 overexpression reversed HG-induced increase in levels of proteins related to fibrosis and the concentration of inflammation factors. The miR-153-3p was revealed to bind with circ-RBM4 and directly targeted nuclear factor I/C (NFIC) in mouse podocytes. Rescue assays indicated that circ-RBM4 attenuated HG-induced fibrosis and inflammation response in mouse podocytes by inhibiting miR-153-3p expression or upregulating NFIC expression. Circ-RBM4 alleviated the renal inflammation and renal fibrosis in DN by targeting the miR-153-3p/NFIC axis.