A Comprehensive Study of the Inhibin/Activin-Family Proteins in Chorioamnionitis

绒毛膜羊膜炎中抑制素/激活素家族蛋白的综合研究

基本信息

批准号：
18591794
负责人：
ABE Yumiko
金额：
$ 1.25万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591794/
关键词：
chorioamnionitis inhibin activin dioxin comprehensive analysis microarray quantitative PCR real-time PCR

项目摘要

Activins are dimeric proteins composed of inhibin/activin beta-subunits, and their biological activities are regulated by inhibins, and activinbinding proteins called follistatins. Recently, the involvement of activins in inflammation and wound healing has been reported. In order to study the role of inhibin/activin family proteins in chorioamnionitis, which is the primary cause of premature rupture of the membranes, we used human amniotic cell culture with the permission of The Internal Review Board and the informed consent of the patients. We studied gene expressions in amniotic epithelial cells by DNA microarray and quantitative PCR analyses, and detected interferon-inducible genes and genes related to collagen synthesis or degradation as dioxin-inducible genes. DNA microarray analysis showed increased expression of the inhibin/activin beta A subunit also. The involvement of activins in the pathology of membranes by dioxins was suggested. In order to study if activins were involved in the inflammation in the compact layer and the fibroblast layer of the membranes, amniotic mesenchymal cells were studied. Tumor necrosis factor-alpha (TNF-alpha) did not increase the inhibin/activin beta B subunit mRNA but did increase the inhibin/activin beta A subunit mRNA. The increase of activin A protein was also shown by enzyme linked immunosorbent assay. Inflammatory cytokine TNF-alpha seemed to stimulate the production of activin A at both mRNA and protein levels in these cells.

激活素是由抑制素/激活素β亚基组成的二聚体蛋白，其生物活性受抑制素和称为卵泡抑素的激活素结合蛋白的调节。最近，有报道称激活素参与炎症和伤口愈合。为了研究抑制素/激活素家族蛋白在绒毛膜羊膜炎（胎膜早破的主要原因）中的作用，我们在内部审查委员会的许可和患者的知情同意下使用了人羊膜细胞培养物。我们通过DNA微阵列和定量PCR分析研究了羊膜上皮细胞中的基因表达，并检测了干扰素诱导基因和与胶原合成或降解相关的基因作为二恶英诱导基因。 DNA 微阵列分析显示抑制素/激活素 β A 亚基的表达也有所增加。有人提出激活素参与二恶英引起的膜病理学。为了研究激活素是否参与胎膜致密层和成纤维细胞层的炎症，对羊膜间充质细胞进行了研究。肿瘤坏死因子-α (TNF-α) 不会增加抑制素/激活素 β B 亚基 mRNA，但会增加抑制素/激活素 β A 亚基 mRNA。酶联免疫吸附测定也显示激活素A蛋白的增加。炎症细胞因子 TNF-α 似乎可以刺激这些细胞中 mRNA 和蛋白质水平上激活素 A 的产生。