Clarification of the mechanism of differentiation from hematopoietic stem cell-derived cells to hepatic stellate cells

我们以前曾阐明，在四氯化碳（CCl_4）诱导的艾弗损伤过程中，造血干细胞来源的细胞能够分化为肝星状细胞（HpSCs）。哪种细胞谱系是HpSC的真正前体仍然未知。我们将从增强型绿色荧光蛋白（EGFP）转基因小鼠中分离的中性粒细胞、单核细胞、嗜酸性粒细胞、B细胞或T细胞，同向转移到CCl_4损伤的非转基因小鼠中。在给予单核细胞的小鼠肝脏中，检测到EGFP^+ HpSCs。这表明一部分单核细胞是HpSC的前体。单核细胞趋化蛋白-1（MCP-1）被认为与单核细胞侵入受损肝脏有关。CCR 2是vICP-1的受体，在单核细胞上表达。我们检测了CCR 2拮抗剂对单核细胞向HpSCs分化的影响，发现该拮抗剂抑制了EGFP^+ HpSCs的数量和损伤肝脏的纤维化面积。

We previously clarified that hematopoietic stem cell-derived cells were abele to differentiate into hepatic stellate cells (HpSCs) during carbon tetrachloride (CCl_4)-induced iver injury. Which lineage of cells are true precursors of HpSCs remains unknown. We idoptively transferred neutrophils, monocytes, eosinophils, B cells, or T cells, which were isolated rom enhanced green fluorescent protein (EGFP)-transgenic mice, into CCl_4-injured non-transgenic nice. In the livers of mice given monocytes, EGFP^+ HpSCs were detected. This suggest that a proportion of monocytes are precursors of HpSCs. Monocyte chemoattractant protein-1 (MCP-1) is bought to be associated with the invasion of monocytes into injured liver. CCR2, a receptor for vICP-1, is expressed on monocytes. We examined the effect of CCR2 antagonist against the lifferentiation of monocytes into HpSCs and found that the antagonist suppressed the number of EGFP^+ HpSCs and the area of fibrosis in injured liver.