Abstract
Sepsis is a systemic inflammatory response caused by infection, and severe sepsis is commonly associated with the development of acute kidney injury (AKI). Accumulating evidence has revealed the implication of circular RNAs in AKI. In this study, we explored the potential engagement and the underlying mechanism of hsa_circ_010157 (circSTRN3) in sepsis-induced AKI. CircSTRN3 levels in HK2 cells and serum samples of patients were determined by RT-PCR. The protein levels of TLR4 (Toll Like Receptor 4), bax (Bcl-2-associated X protein), cleaved caspase 3 and bcl-2 (B-cell lymphoma-2) were detected by Western blotting (WB), and the levels of proinflammatory cytokines were detected by ELISA. The molecular interactions between mir-578/TLR4 and circSTRN3/miR-578 were analyzed by dual luciferase reporter assay as well as RNA pull-down experiment. Lipopolysaccharide (LPS) treated HK2 cells were used as an in vitro model to investigate the functional interaction of circSTRN3/miR-578/TLR4 axis. We found that the expression level of circSTRN3 in patients with sepsis-induced AKI and LPS-induced HK2 cells was higher. Silencing cicrSTRN3 alleviated LPS-induced cell proliferation, and suppressed the inflammatory response and apoptosis in LPS-treated HK2 cells. In contrast, the overexpression of circSTRN3 aggravated the cellular damages induced by LPS treatment. CircSTRN3 targeted miR-578/TLR4 axis to influence the damage effect induced by LPS. miR-578 inhibitor or TLR4 overexpression impaired the rescue effect of circSTRN3 knockdown. These results indicate that circSTRN3 upregulation in sepsis-induced AKI modulates miR-578/TLR4 axis to promote the pathogenesis of AKI, which could serve as future therapeutic targets for AKI treatment.