Circ_0000524/miR‐500a‐5p/CXCL16 axis promotes podocyte apoptosis in membranous nephropathy

Background Podocytes apoptosis is a hallmark of membranous nephropathy (MN). Circ_0000524 has been reported to be associated with patients with MN, whereas the effect of circ_0000524 on podocytes apoptosis and the underlying mechanisms in MN have not been elaborated. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot were performed to detect the expressions of circ_0000524, microRNA‐500a‐5p (miR‐500a‐5p), and C‐X‐C chemokine ligand 16 (CXCL16) in MN tissues and podocytes. Podocyte injury was induced by angiotensin II (AngII). Cell apoptosis was detected by flow cytometry. Caspase‐3 or caspase‐9 activity was evaluated using a caspase‐3 or caspase‐9 activity assay kit, respectively. Dual‐luciferase reporter assay, RNA immunoprecipitation (RIP) and pull‐down assay were used to address the relationship among circ_0000524,miR‐500a‐5p and CXCL16. Results Upregulation of circ_0000524 and CXCL16 and low expression of miR‐500a‐5p were observed in MN tissues. AngII treatment induced the overexpression of circ_0000524 and CXCL16, a decrease of miR‐500a‐5p, and induced cell apoptosis in podocytes. Circ_0000524 negatively modulated the expression of miR‐500a‐5p. Circ_0000524 depletion inhibited podocyte apoptosis, which was rescued by loss of miR‐500a‐5p. miR‐500a‐5p contained the binding sites with CXCL16. Circ_0000524 knockdown hampered CXCL16 expression by upregulating miR‐500a‐5p expression. Additionally, miR‐500a‐5p upregulation suppressed AngII‐induced podocyte apoptosis, which was rescued by enhanced expression of CXCL16. Conclusion Circ_0000524/miR‐500a‐5p/CXCL16 pathway regulated podocyte apoptosis in MN.