BACKGROUND: Effective and timely liver regeneration is pivotal in the prevention of fetal small-for-size syndrome after living donor liver transplantation or split liver transplantation. Our previous study have screened the differential expressed genes between mouse model of liver regeneration with 70% partial hepatectomy (PH) and the normal control using RNA-Seq for the first time. And we found that the ESM1 gene has a significantly higher level in the 70% partial hepatectomy group than that of normal control group. Gene Ontology and enrichment pathway analysis showed ESM1 gene was categorized into NF-κB signal pathway. In this study, we are aiming to examine the effect of ESM1 gene on liver regeneration through activating NF-κB signal pathway and its relevant downstream genes of cyclin D1 in cultured cells.

METHODS: The established mouse liver cell line, Nctc-1469, was cultured in vitro. When ESM1 gene was silenced or overexpressed, cell proliferation was assessed by MTS, cell apoptosis and cell cycle were assessed by flow cytometry, and western blot and RT-qPCR were used to examine the expressions of genes involved in NF-κB signal pathway. Meanwhile, in the cells with ESM1 gene was silenced or overexpressed, the special NF-κB inhibitor PDTC was added, the expressions of genes of NF-kB pathway were examined.

RESULTS: ESM1 knockdown induced cell cycle arrest of G1/S transition, downregulation of NF-κBp50,NF-κBp65,cyclinD1, and upregulation of p21 and p27. It indicated that ESM1 knockdown inhibited cell proliferation and induced apoptosis in mouse hepatocytes. Meanwhile, in the cells with ESM1 gene was silenced, the special NF-κB inhibitor PDTC was added, the expressions of genes of NF-κBp50,NF-κBp65,cyclinD1 were downregulated, and the p21 and p27 were upregulated. On the contrary, ESM1 gene over-expression showed converse results.

CONCLUSIONS: It indicated that ESM1 gene promote hepatocyte proliferation accompanied by decreased apoptosis through NF-κB signal pathway.

CITATION INFORMATION: Zhou J, Ju W, Jiao X, Zhu X, He X. ESM1 Gene Promotes Hepatocyte Proliferation Through NF-κB Signal Pathway. Am J Transplant. 2016;16 (suppl 3).

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