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

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 αsmooth muscle actin (αSMA), CXC chemokine receptor type 4 (CXCR4), extracellular signalregulated kinase (ERK1/2), nuclear factor κB p65 subunit (NFκB p65) and βcatenin were measured by immunohistochemistry, western blotting and reverse transcriptionquantitative 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 αSMA, CXCR4, ERK1/2, NFκB p65 and βcatenin 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 αSMA, NFκB p65 and βcatenin levels were downregulated. The results demonstrated that YGD may induce the differentiation of BMSCs into HLCs to reverse DMNinduced liver cirrhosis; this may be achieved via an upregulation of the SDF1/CXCR4 axis to activate the mitogen activated protein kinase/ERK1/2 signaling pathway.