Pemphigoid gestationis autoantigen, transmembrane collagen XVII, promotes the migration of cytotrophoblastic cells of placenta and is a structural component of fetal membranes
Pemphigoid gestationis autoantigen, transmembrane collagen XVII, promotes the migration of cytotrophoblastic cells of placenta and is a structural component of fetal membranes
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DOI：
10.1016/j.matbio.2007.10.007
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发表时间：
2008-04-01
期刊：
影响因子：
6.9
通讯作者：
Tasanen, Kaisa
中科院分区：
文献类型：
--
作者：
Huilaja, Laura;Hurskainen, Tiina;Tasanen, Kaisa
在妊娠类天疱疮（PG）中，自身抗体靶向胶原XVII，一种半桥粒跨膜蛋白，是皮肤上皮粘附和信号传导的重要元素。我们报告，胶原蛋白XVII表达在妊娠早期和长期合胞体和细胞滋养层细胞的正常胎盘和羊膜上皮细胞。免疫电镜证实了胶原XVII的本地化羊膜上皮的半桥粒。三个PG胎盘的检查显示轻度绒毛炎，但与正常胎盘相比，胶原XVII表达水平或免疫染色信号之间没有差异。在培养的绒毛外滋养层HTR-8/SVneo细胞中也检测到胶原XVII表达，其中胶原XVII表达被PMA和TGF-β 1上调。有趣的是，胶原XVII的细胞迁移结构域Col 15的存在诱导HTR-8/SVneo细胞在迁移测定中的迁移。分析不同孕周的羊水样本显示，在整个妊娠期间，大量的胶原XVII胞外区脱落到羊水中。生化和免疫印迹分析表明，在羊水中的胞外域结构非常相似的培养角质形成细胞产生的胞外域。羊水样本的培养细胞也表达胶原蛋白XVII。我们的研究结果表明，胶原XVII可能有助于胎盘发育过程中绒毛外滋养细胞的入侵，也是羊膜基底膜的完整性所需的。虽然PG的确切病理机制仍不清楚，但PG的临床症状是在妊娠早期胎盘中胶原XVII表达后开始的。(C)2007年Elsevier B. V./国际矩阵生物学学会。All rights reserved.
In pemphigoid gestationis (PG), autoantibodies target collagen XVII, a hemidesmosomal transmembrane protein, which is an important element in cutaneous epithelial adhesion and signalling. We report that collagen XVII is expressed in the first trimester and term syncytial and cytotrophoblastic cells of normal placenta and in epithelial cells of amniotic membrane. Immunoelectron microscopy confirmed the localization of collagen XVII to the hemidesmosomes of amniotic epithelium. Examination of three PG placentas showed mild villitis, but there were no differences between collagen XVII expression levels or immunostaining signals as compared to normal placenta. Collagen XVII expression was also detected in cultured extravillous trophoblast HTR-8/SVneo cells, where collagen XVII expression was upregulated by PMA and TGF-beta 1. Interestingly, the presence of Col 15, the cell migration domain of collagen XVII, induced the migration of HTR-8/SVneo cells in transmigration assay. Analysis of amniotic fluid samples at different gestational weeks revealed that a large quantity of collagen XVII ectodomain was shed into amniotic fluid throughout pregnancy. Biochemical and immunoblotting analysis indicated that the ectodomain in amniotic fluid is structurally very similar to the ectodomain produced by cultured keratinocytes. Cultured cells from amniotic fluid samples also expressed collagen XVII. Our results suggest that collagen XVII may contribute to the invasion of extravillous trophoblasts during placental development and is also required for the integrity of amniotic basement membrane. Although the exact pathomechanism of PG is still largely unknown, the clinical symptoms of PG are initiated after the expression of collagen XVII in placenta during the first trimester of pregnancy. (C) 2007 Elsevier B.V./International Society of Matrix Biology. All rights reserved.