Circ_0000491 Promotes Apoptosis, Inflammation, Oxidative Stress, and Fibrosis in High Glucose-Induced Mesangial Cells by Regulating miR-455-3p/Hmgb1 Axis

Abstract

<b><i>Background:</i></b> Diabetic nephropathy (DN) is a severe microvascular complication of diabetes. Recently, many circular RNAs can exert crucial roles in DN progression. This study intended to explore the role and mechanism of circ_0000491 in DN. <b><i>Methods:</i></b> The DN mouse model was constructed by streptozotocin injection, and the DN cell model was established using high glucose (HG) treatment in mouse mesangial cells (SV40-MES13). The expression of circ_0000491 and microRNA-455-3p (miR-455-3p) was detected by quantitative real-time polymerase chain reaction. Cell apoptosis was evaluated by flow cytometry. The expression levels of high-mobility group box 1 (Hmgb1) protein, apoptosis-related proteins, and fibrosis-related proteins were examined by the Western blot assay. The release of inflammatory cytokines was assessed by enzyme-linked immunosorbent assay. The oxidative stress factors were analyzed by corresponding kits. The predicted interaction between miR-455-3p and circ_0000491 or Hmgb1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. <b><i>Results:</i></b> Circ_0000491 was overexpressed in the DN mouse model and HG-induced SV40-MES13 cells. Knockdown of circ_0000491 weakened HG-induced apoptosis, inflammation, oxidative stress, and fibrosis in SV40-MES13 cells. miR-455-3p was a direct target of circ_0000491, and miR-455-3p inhibition could reverse the role of circ_0000491 silencing in HG-induced SV40-MES13 cells. Moreover, Hmgb1 was a target gene of miR-455-3p, and miR-455-3p played a protective role against HG-induced cell injury by targeting Hmgb1. In addition, circ_0000491 regulated Hmgb1 expression by sponging miR-455-3p. <b><i>Conclusion:</i></b> Circ_0000491 knockdown inhibited HG-induced apoptosis, inflammation, oxidative stress, and fibrosis in SV40-MES13 cells by regulating miR-455-3p/Hmgb1 axis.

circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis

“…circ_0000524 promotes podocyte apoptosis by sponging miR-500a in membranous nephropathy [31]. circRNA_ 13 Oxidative Medicine and Cellular Longevity 010383 sponging miR-135a, circHIPK3 sponging miR-185, circEIF4G2 sponging miR-218, circ_0000491 sponging miR-455-3p, circLRP6 sponging miR-205, and circ_15698 sponging miR-185 contribute to cell death, extracellular matrix production, or renal fibrosis in diabetic nephropathy [32][33][34][35][36][37]. Our group reported that circHIPK3 aggravate renal tubulointerstitial fibrosis by regulating miR-30a [38].…”

Circular RNAs in diabetes and its complications: Current knowledge and future prospects

“…Circ_0000712 potentiated HG-caused apoptosis, inflammation, oxidative stress, and fibrosis in DN by targeting the miR-879-5p and regulating SOX6 expression ( Zhao et al, 2021 ). Similarly, circ_0000491 could regulate Hmgb1 expression by sponging miR-455-3p, thereby exacerbating HG-induced apoptosis, inflammation, oxidative stress, and fibrosis in DN ( Wang et al, 2021b ). In vivo , overexpression of circRNA_010383 downregulated miR-135a function, upregulated transient receptor potential cation channel, subfamily C, and member 1 levels, and inhibited proteinuria and renal fibrosis in DN mice ( Peng et al, 2021 ).…”

miR-455-3p Is Negatively Regulated by Myostatin in Skeletal Muscle and Promotes Myoblast Differentiation

“…Accumulated evidence has shown that miR-455-3p mediates many biological processes. For example, it regulated oxidative stress, mesangial cell apoptosis, and inflammation by targeting Hmgb1 and inhibited liver fibrosis by targeting HDAC2 . Moreover, miR-455-3p levels are greatly related to skeletal muscle mass. , It was postulated that miR-455-3p is engaged in the regulation of MSTN , thereby affecting skeletal muscle development.…”