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  • Title: Heparin-binding epidermal growth factor-like growth factor: a hepatic stellate cell proliferation inducer via ErbB receptors.
    Author: Zhang D, Zhang J, Jiang X, Li X, Wang Y, Ma J, Jiang H.
    Journal: J Gastroenterol Hepatol; 2014 Mar; 29(3):623-32. PubMed ID: 24303948.
    Abstract:
    BACKGROUND AND AIM: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has a proliferative effect on several types of cells. However, the role of HB-EGF on hepatic stellate cells (HSCs) is not clear. The present study is to investigate the regulatory effects of HB-EGF on HSC proliferation and apoptosis. METHODS: Activated primary rat HSCs and two HSC cell lines (human LX2 and rat T6) were used in this study. Four inhibitors (CRM197 to HB-EGF, AG1478 to epidermal growth factor receptor [EGFR], PD98059 to mitogen-activated kinase, and LY294002 to phosphatidylinositol 3-kinase) were employed to verify the pathway of HB-EGF on cell proliferation and apoptosis. RESULTS: HB-EGF expression was significantly increased in activated HSCs. HB-EGF increased the expressions of phospho-EGFR and ErbB4 receptors, the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. Consequently, HB-EGF stimulated HSC proliferation and suppressed HSC apoptosis. Each individual inhibitor specifically inhibited the correlated receptor or enzyme and inhibited HSC proliferation and induced its apoptosis. CONCLUSIONS: HB-EGF promotes HSC proliferation via activation of the EGFR and ErbB4 receptors and, subsequently, via activation of ERK and Akt. Any blockage in the chain obstructs the flow from HB-EGF to HSC proliferation. Therefore, HB-EGF is a potential therapeutic target in liver fibrosis.
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