Bone marrow endothelial progenitor cells activate hepatic stellate cells and aggravate carbon tetrachloride induced liver fibrosis in mice via paracrine factors.

ABSTRACT: OBJECTIVES:Bone marrow derived endothelial progenitor cells (BM-EPCs) are increased in chronic liver disease (CLD). Their role in hepatic fibrosis and regeneration remains an area of intense studies. We investigated the migration and secretory functions of BM-EPCs in fibrotic mice liver. MATERIALS AND METHODS:Bone marrow cells from C57BL6-GFP mice were transplanted into the femur of irradiated C57BL6 mice, followed by CCl4 doses for 8 weeks, to develop hepatic fibrosis (n = 36). Transplanted C57BL6 mice without CCl4 treatment were used as controls. EPCs were analyzed in BM, blood and liver by flow cytometry and immunofluorescence. VEGF and TGF-? were analysed in the hepatic stellate cells (HSCs) and BM-EPCs co-cultures using ELISAs. RESULTS:There was a significant migration of EPCs from BM to blood and to the liver (P ? 0.01). Percentage of GFP+ CD31+ EPCs and collagen proportionate area was substantially increased in the liver at 4th week of CCl4 dosage compared to the controls (19.8% vs 1.9%, P ? 0.05). Levels of VEGF (533.6 pg/ml) and TGF-? (327.44 pg/ml) also increased significantly, when HSCs were treated with the EPC conditioned medium, as compared to controls (25.66 pg/ml and 5.87 pg/ml, respectively; P ? 0.001). CONCLUSIONS:Present findings suggest that BM-EPCs migrate to the liver during CCl4-induced liver injury and contribute to fibrosis.

SUBMITTER: Garg M 

PROVIDER: S-EPMC6529081 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature