Potentiality of endothelial to mesenchymal transition in ex-vivo rarely contribute to hepatic fibrogenesis in vivo

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BACKGROUND AND AIMS: Recent studies have reported the possibilities of endothelial to messenchymal transition (EndMT) in several tissues, which means endothelial cells migrating into fibrotic tissue exhibit a myofibroblast-like phenotype and may participate in the progression of tissue fibrosis. However, their contribution to fibrosis in liver has not been fully verified yet. We revisited this issue by using liver fibrosis models introduced into transgenic collagen reporter mice. METHODS: Bone marrow of Tie2-Cre, CAG-CAT, GFP double transgenic mice was replaced by cells obtained from wild-type mice harboring endothelial cell-specific Tie2 gene linked to enhanced green fluorescent protein (EGFP) gene. Liver fibrosis was introduce d into those mice by repeated carbon tetrachloride injections. EGFP expression was assessed by confocal microscopic examination.RESULTS: Endothelial cells performed mesenchymal transition during primary culture on plastic. In Tie2-Cre, CAG-CAT, GFP double transgenic mice, endothelial cells express EGFP, at the same time, a large number of EGFP-positive immunocompetent cells were observed. In contrast, Tie2-Cre, CAG-CAT, GFP double transgenic mice whose bone marrow was replaced by cells obtained from wild-type mice have no EGFP positive cells but endothelial cell. Though, double transgenic mice observed many EGFP-positive cells at liver fibrotic area, there were few EGFP-positive cell in double transgenic mice whose bone marrow was replaced by wild-type mice. CONCLUSIONS: By using a specific and sensitive experimental system, which detects cells whose roots were endothelial cells excrusively, we conclude an unexpectedly limited role of EndMT during CCl4induced liver fibrogenesis.