MiR-340 suppresses CCl4-induced acute liver injury through exerting anti-inflammation targeting Sigirr

Acute liver injury (ALI) can be caused by ischemia, viral infection, immune disorders and exogenous substances. Finding novel drugs and methods to treat liver injury is still one of the problems to be precipitously solved in clinical liver diseases. Recent studies have verified that microRNA-340 (miR-340) and the Single immunoglobin interleukin-1 (IL-1)-related receptor (Sigirr) display extensive anti-inflammatory effects against inflammatory diseases. However, their protection against inflammation in ALI is unclear. The purpose of this study was to investigate the regulated mechanism of miR-340 targeting Sigirr on ALI.

Firstly, the expressions of miR-340 and Sigirr in different time of inflammatory Kupffer cells (KCs) were detected. Lipopolysaccharide (LPS) was employed in activating the KCs inflammation, and tetrachloromethane (CCl4) was performed to induce liver injury. Then miR-340 mimic and inhibitor were used to up-regulate or down-regulate the function of miR-340 to explore anti-inflammation function to ALI via the target of Sigirr.

The study results exhibited that the expressions of miR-340 and Sigirr were markedly decreased in LPS-induced KCs inflammation, and CCl4 induced the development of ALI. Besides, the overexpression of miR-340 could alleviate the inflammation of LPS induction in KCs via promoting Sigirr. Moreover, miR-340 and Sigirr rescue significantly reduced liver function and tissue lesion by employing miR-340 mimic.

MiR-340 decreases KC inflammation via enhancing Sigirr, but accumulating miR-340 prevents inflammation damage and ameliorates ALI. In addition, increased miR-340 and Sigirr may become novel targets for the therapy of ALI in the future.