Circ_LARP4 regulates high glucose-induced cell proliferation, apoptosis, and fibrosis in mouse mesangial cells.

Abstract

The current study aimed to investigate the role and underlying mechanisms of circ_LARP4 in diabetic nephropathy (DN). Here, mouse mesangial cells (SV40-MES13) were cultured with 30mM glucose to establish a DN cellular model. The qRT-PCR results indicated that circ_LARP4 expression was downregulated in the DN cellular model compared to that in the control cells. As determined by an MTT assay, circ_LARP4 overexpression via the circ_LARP4 overexpression (OE) plasmids inhibited the cell proliferation rate. As determined by an Annexin V/PI kit and flow cytometry, circ_LARP4 overexpression increased the cell apoptosis rate. As measured by Western blot, circ_LARP4 overexpression enhanced BAX expression but reduced Bcl-2 expression, also suggesting an enhancement of cell apoptosis. Moreover, regarding cell fibrosis, circ_LARP4 overexpression reduced the mRNA levels of fibrosis markers, including fibronectin, collagen I and collagen IV. Interestingly, miR-424 was found to be reduced in the DN cellular model after transfection with the circ_LARP4 OE plasmids. In addition, restoration of miR-424 expression with the miR-424 mimics reversed the negative effects of circ_LARP4 overexpression on cell proliferation and fibrosis. In conclusion, circ_LARP4 was lower in the DN cellular model than in normal cells, and circ_LARP4 overexpression resulted in decreased cell proliferation and cell fibrosis but increased cell apoptosis in the DN cellular model by sponging miR-424.