CircRNA-0013747 induces mesangial cell proliferation in IgA nephropathy by targeting the Warburg effect via miR-330- 3p/PKM2 signaling

Abstract

Abstract Aberrant mesangial cell proliferation is a prevailing histopathological feature of immunoglobulin A nephropathy (IgAN) and is the primary driver of glomerular sclerosis and impaired renal function in IgAN patients. Prior research has revealed that PKM2-mediated aerobic glycolysis (the Warburg effect) frequently promotes mesangial cell growth and contributes to the development of various acute and chronic kidney diseases. However, the expression and functionality of PKM2 in IgA nephropathy, as well as the underlying molecular mechanisms governing its abnormal expression, remain elusive. Circular RNAs, a subset of noncoding RNAs, have garnered increasing attention due to mounting evidence of their pivotal roles in the initiation and progression of numerous disorders. The present study aimed to explore the effects of circRNA_0013747 on IgAN and the potential underlying mechanisms. The results indicated notable overexpression of circRNA_0013747 in lipopolysaccharide (LPS)-treated human mesangial cells (HMCs) and kidney biopsy samples from IgAN patients. CircRNA_0013747 was shown to facilitate mesangial cell proliferation and activate PKM2-mediated aerobic glycolysis, although these effects were mitigated by an increase in miR-330-3p. Mechanistically, circRNA_0013747 physically interacted with microRNA-330-3p (miR-330-3p) and hindered its function by directly binding to it. These findings imply that circRNA_0013747 can enhance glycolysis and proliferation in mesangial cells by modulating the miR-330-3p/PKM2 signaling pathway. In conclusion, the present results underscore the possibility of circRNA_0013747 serving as a promising therapeutic target for IgAN, suggesting new prospects for treating this disease.