Regulation loss of mesangial cell function leading to irreversible, glomerular sclerosis.

在肾小球中，毛细血管内区域是一个封闭的空间，被肾小球基底膜包围，基底膜由毛细血管腔、内皮细胞(ECs)、系膜细胞(MC)和系膜基质组成。我们的工作假设是，内在细胞和/或基质的形态和功能调节的丧失可能导致MCs功能障碍，导致毛细血管内区MCs增殖、细胞外基质合成增强、MCs迁移和系膜插入等病理变化。在文部科研基金(1994年06670215号)的资助下，我们建立了大鼠主动脉内皮细胞的培养方法。MicrovascRes50：113,1995)。利用这些内皮细胞，我们在共培养体系中检测了存在于大鼠系膜细胞表面的潜在功能分子。在上述资助的研究期间(1994-1995)，我们获得了以下结果：1.培养的大鼠肾小球系膜细胞上存在一些与Thy-1.1抗原相关的特异性分子。其中一种细胞有一个特异性表位，该表位集中在共培养体系中与内皮细胞相对的MC一侧。2.将Thy-1.1基因导入COS细胞，可用于相关表位的分析(T Oite等)。Exp Nephrol 1996，在印)。3.向单侧肾切除大鼠静脉注射抗肾小球硬化素表位的单抗建立进行性肾小球硬化动物模型(程庆林等临床实验免疫102：181,1995)。4.大鼠肾小球I型和III型胶原在蛋白和mRNA水平均有表达增加。

In the glomerulus, the endocapillary region is a closed space surrouded by the glomerular basement membrane comprised of a capillary lumen, endothelial cells (ECs), mesangial cells (MCs), and mesangial matrices. Our working hypothesis is that loss of morphological and functional regulation by intrinsic cells and/or matrices may induce MCs dysfunction, leading to the pathological changes such as proliferation, enhanced extracellular matrix synthesis, MCs migration and mesangial interposition in the endocapillary region. By the aid of research grant (No.06670215,1994) from the Ministry of Education, Science and Culture, we were able to establish the culture method of rat aortic ECs (T Oite el al. MicrovascRes50 : 113,1995). Using these ECs, we have examined the potentially functional moleculepresent on rat MCs surface in coculture system. During the research period (1994-1995) supported by the above described grant, we have obtained the following results ; 1.Some specific molecules, associated with Thy-1.1 antigen was preseent on cultured rat MCs. One ofthem had a specific epitope which was concentrated on the side of the MCs that faces with ECs in coculture system .2.COS cells transfected with cDNA for Thy-1.1 ware able to be used for analysis of the relevant epitope (T Oite etal. Exp Nephrol 1996, in press) . 3.An animal model of progressive glomerulosclerosis was developed by administeringa single iv injection of monoclonal antibody against this epitope to unilaterally nephrectomized rats (Cheng QL et al Clin exp Immunol 102 : 181,1995). 4.Expression of collagen type I and III was increased in glomeruli from these rats at the levels of protein and mRNA.