Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis
Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis
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DOI：
10.1016/j.jhep.2009.01.028
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发表时间：
2009-06-01
影响因子：
25.7
通讯作者：
Li, Liying
中科院分区：
文献类型：
--
作者：
Li, Changyong;Kong, Yaxian;Li, Liying
背景/目的：肌成纤维细胞在肝纤维化的发病机制中发挥核心作用。最近在纤维化肝脏中发现了骨髓（BM）来源的肌成纤维细胞。然而，人们对控制它们在体内动员的机制知之甚少。在这里，我们证实骨髓间充质干细胞（BMSCs）可以迁移到受损的肝脏并分化为肌成纤维细胞。我们还研究了肝损伤后骨髓间充质干细胞归巢的机制。方法：对ICR小鼠进行致死性照射，并接受来自增强型绿色荧光蛋白转基因小鼠的骨髓移植。使用四氯化碳或胆管结扎来诱导肝纤维化。通过免疫荧光染色检查纤维化肝组织以鉴定骨髓来源的肌成纤维细胞。结果：BMSCs对纤维化肝中的肌成纤维细胞群有显着贡献。此外，体内和体外分析表明，BMSCs 归巢至受损肝脏是对肝脏和 BM 之间 1-磷酸鞘氨醇 (S1P) 梯度的反应。此外，S1P触发的BMSCs迁移需要S1P受体3型（S1P（3））。结论：S1P通过S1P（3）受体使BMSCs归巢来介导肝纤维化，这可能是通过抑制S1P形成和/或受体激活来治疗肝纤维化的新靶点。 (C) 2009 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Background/Aims: Myofibroblasts play a central role in the pathogenesis of liver fibrosis. Myofibroblasts of bone marrow (BM) origin have recently been identified in fibrotic liver. However, little is known about the mechanism that controls their mobilization in vivo. Here we confirmed that BM mesenchymal stem cells (BMSCs) can migrate to the damaged liver and differentiate into myofibroblasts. We also investigated the mechanism underlying the homing of BMSCs after liver injury.Methods: ICR mice were lethally irradiated and received BM transplants from enhanced green fluorescent protein transgenic mice. Carbon tetrachloride or bile duct ligation was used to induce liver fibrosis. The fibrotic liver tissue was examined by immunofluorescent staining to identify BM-derived myofibroblasts.Results: BMSCs contributed significantly to myofibroblast population in fibrotic liver. Moreover, analysis in vivo and in vitro suggested that homing of BMSCs to the damaged liver was in response to sphingosine 1-phosphate (S1P) gradient between liver and BM. Furthermore, S1P receptor type 3 (S1P(3)) was required for migration of BMSCs triggered by S1P.Conclusions: S1P mediates liver fibrogenesis through homing of BMSCs via S1P(3) receptor, which may represent a novel therapeutic target in liver fibrosis through inhibiting S1P formation and/or receptor activation. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.