The protective effect of bone marrow-derived mesenchymal stem cells in liver ischemia/reperfusion injury via down-regulation of miR-370

Objective(s): Liver transplantation is the most important therapy for end-stage liver disease and ischemia reperfusion (I/R) injury is indeed a risk factor for hepatic failure after grafting. The role of miRNAs in I/R is not completely understood. The aim of this study was to investigate the potential protective role of the mesenchymal stem cells (MSCs) and ischemic preconditioning on miR-370 expression and tissue injury in hepatic I/R injury. Materials and Methods: In this study, 24 BALB/c mice were divided into 4 groups, including sham, I/R, I/R mouse that received MSCs (I/R+MSC) and ischemia preconditioning (IPC) The expression levels of hepatic miR-370, Bcl2 and BAX in male BALB/c mice in different groups including hepatic I/R, hepatic I/R received MSCs, and hepatic I/R with IPC were assessed by quantitative real-time PCR. The effect of miR-370 on hepatic I/R was investigated by serum liver enzyme analysis and histological examination. Results: The expression of miR-370 was significantly up-regulated in the mice subjected to hepatic I/R injury as compared with the sham operated mice. Injection of MSCs led to the down-regulation of the serum liver enzymes, expression of miR-370 and BAX, up-regulation of Bcl2 as well as the improvement of hepatic histological damage. IPC led to similar results, but the difference was not significant. Conclusion: Our data suggest that miR-370 affected the Blc2/BAX pathway in hepatic I/R injury, and down- regulation of miR-370 by BM-MSCs efficiently attenuated the liver damage.

کلیدواژه ها:

Apoptosis ، Bcl2 ، Bax ، Ischemia reperfusion injury ، Mesenchymal stem cells ، microRNA 370