Effect of Yi Guan Jian decoction on differentiation of bone marrow mesenchymalstem cells into hepatocyte-like cells in dimethylnitrosamine-induced liver cirrhosis in mice.

Abstract

Yi Guan Jian decoction (YGD) may induce the differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocyte-like cells (HLCs); however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate this process. To do this, a dimethylnitrosamine (DMN)-induced liver cirrhosis mouse model was established. The mice from the model group were randomly divided into three subgroups: i) Negative control, ii) hepatocyte growth factor and iii) YGD. The overall health, liver function and histological alterations were monitored. The expression of α-smooth muscle actin (α-SMA), C-X-C chemokine receptor type 4 (CXCR4), extracellular signal-regulated kinase (ERK1/2), nuclear factor κB p65 subunit (NF-κB p65) and β-catenin were measured by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. Following administration of DMN, the overall health of the mice significantly decreased, with an increase in pathological developments and liver damage resulting in a decrease in liver function. Immunohistochemistry revealed that the expression of α-SMA, CXCR4, ERK1/2, NF-κB p65 and β-catenin was upregulated. Following treatment with YGD, the overall health, liver function and pathology improved. The mRNA and protein expression levels of CXCR4 and ERK1/2 were upregulated, where as α-SMA, NF-κB p65 and β-catenin levels were downregulated. The results demonstrated that YGD may induce the differentiation of BMSCs into HLCs to reverse DMN-induced liver cirrhosis; this may be achieved via an upregulation of the SDF-1/CXCR4 axis to activate the mitogen activated protein kinase/ERK1/2 signaling pathway.