Circ_0000181 regulates miR-667-5p/NLRC4 axis to promote pyroptosis progression in diabetic nephropathy

Abstract

AbstractOur previous research demonstrated that NOD-like receptor family CARD domain-containing protein 4 (NLRC4) inflammasome was overexpressed in renal tissues of patients with diabetic nephropathy (DN). This study further investigated the effect of circRNAs-miRNAs interaction on NLRC4 and their potential mechanisms. DN mice models were first established using STZ. Then, pyroptosis related marker expression was detected using qPCR, western blot (WB), and immunohistochemistry analysis. After that, differentially expressed circRNAs, miRNAs, and mRNAs were investigated using next-generation sequencing. Additionally, the function and potential mechanism of circ_0000181 and miR-667-5p on pyroptosis were measured in vitro DN cell model using MTS, WB, and Enzyme-linked immunosorbent assay. There was an apparent elevation of NLRC4, Caspase1, IL-1β, and IL-18 levels in DN mice. The next-generation sequencing results revealed that there were 947 circRNAs and 390 miRNAs significantly different between the DN and sham kidney tissue, of which circ_0000181 and miR-667-5p had potential targeting effects with NLRC4. Dual-luciferase and functional rescue experiments demonstrated that circ_0000181 promoted NLRC4 inflammasome activation via competitive sponge of miR-667-5p, promoted the release of IL-1β and IL-18, and caused pyroptosis. Altogether, circ_0000181 regulates miR-667-5p/NLRC4 axis to promote pyroptosis progression in DN.