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

在肾小球中，毛细血管内区域是由肾小球基底膜包围的封闭空间，所述肾小球基底膜由毛细血管腔、内皮细胞（EC）、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会诱导MC功能障碍，导致病理变化，如增殖，细胞外基质合成增强，MC迁移和系膜内毛细血管区的干预。本研究利用文部科学省科研基金（No.06670215，1994）建立了大鼠主动脉内皮细胞的培养方法（T Oite et al.MicrovascRes50：113，1995）。利用这些内皮细胞，我们在共培养系统中检测了大鼠MCs表面的潜在功能分子。在上述基金资助的研究期间（1994-1995），我们获得了以下结果：1.培养的大鼠MC上存在与Thy-1.1抗原相关的特异性分子。2.转染Thy-1.1 cDNA的COS细胞可用于相关抗原表位的分析（T Oite埃塔尔Exp Nephrol 1996，出版中）。3.通过单次静脉注射抗该表位的单克隆抗体给单侧肾切除大鼠建立了进行性肾小球硬化的动物模型（Cheng QL et al Clin exp Immunol 102：181，1995）。4.在蛋白质和mRNA水平上，这些大鼠肾小球中I型和III型胶原的表达增加。

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.