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.