Circ_0001806 relieves LPS-induced HK2 cell injury by regulating the expression of miR-942-5p and TXNIP

Abstract

Sepsis is a systemic inflammatory disease that can cause a variety of diseases, including septic acute kidney injury (AKI). Circular RNAs (circRNAs) are believed to be involved in the development of this disease. This study aims to clarify the function of circ_0001806 in lipopolysaccharide (LPS)-induced HK2 cell model and its related mechanisms. Circ_0001806 was up-regulated in septic AKI serum specimens and LPS-induced HK2 cells. Circ_0001806 knockdown promoted cell proliferation and restrained apoptosis, inflammation and oxidative stress in LPS-induced HK2 cells. In mechanism, circ_0001806 can be used as a sponge for miR-942-5p, and miR-942-5p can directly target TXNIP. Functional experiments revealed that the miR-942-5p inhibitor could reverse the alleviating effect of circ_0001806 knockdown on LPS-induced HK2 cell injury, and TXNIP addition can also reverse the inhibitory effect of miR-942-5p overexpression on LPS-induced HK2 cell injury. In addition, circ_0001806 regulated TXNIP expression through sponging miR-942-5p. Besides, exosome-derived circ_0001806 was upregulated in LPS-induced HK2 cells, while was downregulated by GW4869. The results showed that circ_0001806 knockdown could reduce LPS-induced HK2 cell injury by regulating TXNIP expression via targeting miR-942-5p, indicating that circ_0001806 might be an important biomarker for alleviating sepsis-related AKI. This might provide therapeutic strategy for the treatment of sepsis.

Keywords: AKI; Sepsis; TXNIP; circ_0001806; miR-942-5p.