SgIGSF is a novel biliary-epithelial cell adhesion molecule mediating duct/ductule development
SgIGSF is a novel biliary-epithelial cell adhesion molecule mediating duct/ductule development
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DOI：
10.1002/hep.21501
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发表时间：
2007-03-01
期刊：
影响因子：
13.5
通讯作者：
Yokozaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Ito, Akihiko;Nishikawa, Yuji;Yokozaki, Hiroshi
生精免疫球蛋白超家族（SgIGSF）是一种细胞间粘附分子，属于凝集素样家族。在筛选其组织分布时，发现其在胎儿肝脏中表达，而在成人肝脏中不表达。在本研究中，我们通过免疫组织化学和Western印迹分析来检测发育和再生肝脏中哪些细胞表达SgIGSF。在发育中的小鼠肝脏中，SgIGSF表达在围产期短暂上调，并仅限于胆管上皮细胞（BEC）的侧膜。在再生的大鼠肝脏2-乙酰氨基芴/部分肝切除模型，SgIGSF被检测到专门在卵圆细胞排列在导管和小梁模式的第二周posthepatectomy。在人类肝脏中，胎儿和新生儿胆管和黄疸胆管SgIGSF明显阳性，而无病成人胆管阴性。为了研究SgIGSF在胆管/小管形成中的作用，我们使用了一种体外模型，其中大鼠肝细胞聚集体包埋在含有胰岛素和表皮生长因子的胶原凝胶中，在第一周内延伸上皮片和突起，并在一个月内形成小管。突起和小管细胞持续阳性SgIGSF和细胞角蛋白19，BEC标记。当在功能阻断性抗SgIGSF抗体存在下开始聚集体培养时，每个聚集体的上皮突起的数量减少了80%。结论：我们认为SgIGSF是一种新型的功能性BEC粘附分子，在活跃的胆管/小管形成过程中表达时间有限。
Spermatogenic immunoglobulin superfamily (SgIGSF) is an intercellular adhesion molecule of the nectin-like family. While screening its tissue distribution, we found that it was expressed in fetal liver but not adult liver. In the present study, we examined which cells in developing and regenerating liver express SgIGSF via immunohistochemistry and Western blot analysis. In developing mouse liver, SgIGSF expression was transiently upregulated at perinatal ages and was restricted to the lateral membrane of biliary epithelial cells (BECs). In regenerating rat livers from the 2-acetylaminofluorene/partial hepatectomy model, SgIGSF was detected exclusively in oval cells that aligned in ductal and trabecular patterns by the second week posthepatectomy. In human livers, fetal and newborn bile ducts and cirrhotic bile ductules were clearly positive for SgIGSF, whereas disease-free adult bile ducts were negative. To investigate the role of SgIGSF in bile duct/ductule formation, we used an in vitro model in which rat hepatocyte aggregates embedded in collagen gels containing insulin and epidermal growth factor extend epithelial sheets and processes in the first week and form ductules within a month. The process and ductular cells were continuously positive for SgIGSF and cytokeratin 19, a BEC marker. When the aggregate culture was started in the presence of a function-blocking anti-SgIGSF antibody, the number of epithelial processes per aggregate was reduced by 80%. Conclusion: We propose that SgIGSF is a novel and functional BEC adhesion molecule that is expressed for a limited time during active bile duct/ductule formation.