Acute liver failure (ALF) is a disease resulted from diverse etiology, which generally leads to a rapid degenerated hepatic function. However, transplantation bone marrow-derived mesenchymal stem cells (BMSCs) transplantation has been suggested to relieve ALF. Interestingly, microRNA-214 (miR-214) could potentially regulate differentiation and migration of BMSCs. The present study aims to inquire whether miR-214 affects therapeutic potential of BMSCs transplantation by targeting PIM-1 in ALF. 120 male Wistar rats were induced as ALF model rats and transplanted with BMSCs post-alteration of miR-214 or PIM-1 expression. Further experiments were performed to detect biochemical index (alanine aminotransferase [ALT], aspartate transaminase [AST], total bilirubin [TBiL]), and expression of miR-214, PIM-1, hepatocyte growth factor (HGF), caspase 3, tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in rat serum. Apart from the above detection, apoptosis of hepatocytes and Ki67 protein expression in hepatic tissues of rats were additionally assessed. After BMSCs transplantation with miR-214 inhibition, a decreased expression of ALT, AST, and TBiL yet an increased expression of HGF was shown, coupled with a decline in the expression of caspase 3, TNF-α, and IL-10. Meanwhile, alleviated hepatic injury and decreased apoptotic index of hepatic cells were observed and the positive rate of Ki67 protein expression was significantly increased. Moreover, miR-214 and caspase 3, TNF-α, and IL-10 decreased notably, while PIM-1 was upregulated in response to miR-214 inhibition. Strikingly, the inhibition of PIM-1 reversed effects triggered by miR-214 inhibition. These findings indicated that downregulation of miR-214 improves therapeutic potential of BMSCs transplantation by upregulating PIM-1 for ALF.
Keywords: PIM-1; acute liver failure; bone marrow-derived mesenchymal stem cells; microRNA-214; therapeutic potential; transplantation.
© 2019 Wiley Periodicals, Inc.