Protective role of microRNA-9-5p in oxygen glucose deprivation/reperfusion-induced injury in liver sinusoidal endothelial cell

Abstract Background: Maintenance of the function and survival of liver sinusoidal endothelial cells (LSECs) play a crucial role in hepatic ischemia/reperfusion (I/R) injury, a major cause of liver impairment during surgical treatment. Emerging evidence indicate a critical role of microRNAs in I/R injury. This study aims to investigate whether miR-9-5p exert a protective effect on LSECs in vitro . Methods: We transfected LSECs with miR-9-5p mimic or mimic NC. LSECs were treated with oxygen and glucose deprivation (OGD, 5% CO2 and 95% N2), followed by glucose-free DMEM medium for 6 h, and high-glucose (HG, 30 mmol/L glucose) DMEM medium for 12 h. The biological role of miR-9-5p in I/R-induced LSEC injury was determined. Results: In the in vitro model of OGD/HG injury in LSECs, the expression levels of miR-9-5p were significantly downregulated and those of CXC chemokine receptor-4 (CXCR4) upregulated. LSEC I/R injury led to deteriorated cell death, enhanced oxidative stress and excessive inflammatory response. Mechanistically, we showed that miR-9-5p overexpression significantly upregulated both mRNA and protein levels of CXCR4, followed by rescue of LSECs, ameliorated inflammatory response, and deactivation of pro-apoptotic signaling pathways. Conclusion: miR-9-5p promotes LSEC survival and inhibits apoptosis and inflammatory response in LSECs following OGD/HG injury via downregulation of CXCR4.