Participation of bone marrow cells in biliary fibrosis after bile duct ligation
Participation of bone marrow cells in biliary fibrosis after bile duct ligation
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DOI：
10.1111/j.1440-1746.2006.04708.x
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发表时间：
2007-11-01
影响因子：
4.1
通讯作者：
Gotoh, Mitsukazu
中科院分区：
文献类型：
--
作者：
Asawa, Sadanori;Saito, Takuro;Gotoh, Mitsukazu
背景与目的：骨髓源性细胞参与了慢性损伤后继发性肝纤维化的形成过程。然而，目前尚不清楚这种事件在急性纤维化模型中发生的速度。本研究的目的是使用表达绿色荧光蛋白（GFP）的骨髓细胞来确定骨髓细胞在小鼠胆管结扎后快速纤维化中的作用。方法：全身照射后，将来自绿色荧光蛋白（+/-）小鼠的1 × 10（6）供体全骨髓细胞通过尾静脉移植到C57 BL/6受体中。骨髓移植后4周，嵌合小鼠进行胆总管结扎，这些动物的肝脏进行组织学检查胆管结扎后，使用抗成纤维细胞特异性蛋白（FSP）-1抗体和抗α-平滑肌肌动蛋白（α-SMA）antibody.Results：胆管周围纤维化的成纤维细胞特异性蛋白阳性细胞组成的组织学表现早在第7天。大部分纤维化细胞呈绿色荧光蛋白阴性，但也有相当数量的细胞呈绿色荧光蛋白阳性，部分细胞还呈抗FSP或α-SMA阳性。骨髓来源的细胞分化成活化的成纤维细胞和成肌纤维细胞样表型发生在胆管结扎后的管周纤维化的非常早期过程中，提示通过抑制骨髓细胞向肝脏的迁移来预防胆道纤维化的新策略。
Background and Aim: Bone marrow derived cells are involved in the process of hepatic fibrosis secondary to chronic injury. However, it is not yet known how quickly this event occurs in acute fibrosis models. The purpose of this study was to determine the role of bone marrow cells in rapid fibrosis following bile duct ligation in mice using green fluorescent protein (GFP) expressing bone marrow cells.Methods: After whole body irradiation, 1 x 10(6) donor whole bone marrow cells from green fluorescent protein(+/-) mice were transplanted into C57BL/6 recipients via the tail vein. Four weeks after bone marrow transplantation, chimeric mice were subjected to common bile duct ligation, and livers of these animals were histologically examined after bile duct ligation using anti-fibroblast specific protein (FSP)-1 antibody and anti-alpha-smooth muscle actin (alpha-SMA) antibody.Results: Periductal fibrosis consisting of fibroblast specific protein-positive cells was demonstrated histologically as early as day 7. Most of the fibrotic cells were green fluorescent protein-negative, however, a significant number of cells were green fluorescent protein-positive and some were also anti-FSP or alpha-SMA-positive.Conclusion: Differentiation of bone marrow derived cells into activated fibroblast and myofibroblast-like phenotypes occurs in the very early course of periductal fibrosis following bile duct ligation, suggesting a new strategy for prevention of biliary fibrosis by inhibiting migration of bone marrow cells to liver.