The roles of IP10 in liver regeneration and tissue repair are cell type dependent

Abstract

INTRODUCTION AND AIM: Impairment of liver regeneration is the major consequence resulted from acute phase marginal liver graft injury. Understanding of key players in liver regeneration is crucial to develop potential treatments such as stem cell therapy. IFN-inducible protein 10 (IP10) was reported to have controversial roles in liver regeneration. Here, we aimed to investigate the role of IP10 in marginal graft regeneration, and to explore its effect on bone marrow derived mesenchymal stem cells (BM-MSC) proliferation. METHODS: The expression of hepatic IP10 and hepatocyte proliferation was assessed at day 2, 4 and 7 post-transplantation in a rat orthotopic liver transplantation model using normal or fatty small-for-size grafts. To investigate the role of IP10 in hepatocyte proliferation and liver regeneration, IP10-/- and CXCR3-/- (IP10 receptor) mice with or without fatty liver were subjected to major hepatectomy and partial hepatic ischemia/reperfusion injury. Mice hepatocyte proliferation, expressions of HGF and vascular endothelial growth factor were compared among the different groups. To explore the role of IP10 on BM-MSC, we compared cell proliferation, differentiation and cell cycle of the BM-MSCs from IP10-/-, CXCR3-/- and wild type mice. RESULTS: Intrahepatic IP10 expression was signifi cantly reduced in small-for-size fatty graft in comparison to normal graft (day 2: 2.48 vs 8.22 folds, p < 0.05) and correlated with lower hepatocyte proliferation (day 2: 6.5/HPF vs 32/HPF, p < 0.01) after transplantation. Signifi cant impairment in hepatocyte proliferation in IP10-/-and CXCR3-/- mice was also detected.