Premium
Downregulation of microRNA‐214 improves therapeutic potential of allogeneic bone marrow–derived mesenchymal stem cell by targeting PIM‐1 in rats with acute liver failure
Author(s) -
Yang Juan,
Li Rui,
Zhao Dan,
Zheng Sheng
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28560
Subject(s) - mesenchymal stem cell , transplantation , hepatocyte growth factor , downregulation and upregulation , tumor necrosis factor alpha , bone marrow , stem cell , cancer research , aspartate transaminase , apoptosis , alanine transaminase , medicine , immunology , chemistry , alkaline phosphatase , biology , pathology , microbiology and biotechnology , biochemistry , receptor , gene , enzyme
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.