权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

progressive mesangial cell proliferation and expansion in mice overepxressed mesangium-predominant serine protease inhibitor, megsin,

过度表达系膜为主的丝氨酸蛋白酶抑制剂 megsin 的小鼠进行性系膜细胞增殖和扩张

基本信息

批准号：
13671129
负责人：
INAGI Reiko
金额：
$ 2.69万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671129/
关键词：
mesangial cells megsin serpin serine protease glomerulonephritis mesangial matrix transgenic mice メサンギウム基質

项目摘要

We employed mouse molecular genetic approaches and overexpressed human megsin gene in mice. Some megsin transgenic mice exhibited glomerular morphological changes at 40 weeks of age. The pathological changes included increased number of cells in the mesangial area and an expansion of mesangial matrix. Furthermore, when we induced anti-glomerular basement membrane (GBM) nephritis in wild type and megsin transgenic mice, mesangial expansion persisted only in the transgenic mice. The glomerular lesions in megsin transgenic mice were accompanied by an augmented immune complex deposition together with immunoglobulins and complement. It is unlikely that a primary mechanism of immune complex (IC) deposition in these mice was augmented production, because the levels of circulating IC in transgenic mice were at best trivial. The explanation of this phenomenon should be found in a decreased capacity of mesangial cells to clear macromolecules such as immune complexes. We speculate that overexpression of megsin, a mesangium predominant gene, might lead to mesangial dysfunction, impair the degradation and disposal of IC, and alter the microenvironment of mesangial matrix. We performed hemi-nephrectomy to accelerate glomerular injury in megsin transgenic mice. Hemi-nephrectomized transgenic mice developed focal segmental mesangial expansion, which was associated with proteinuria. Hemi-nephrectomized model of this transgenic mice might serve as a tool to investigate mechanisms of glomerular disease.

我们利用小鼠分子遗传学方法，在小鼠体内过表达了人巨噬蛋白基因。部分转基因小鼠在40周龄时出现肾小球形态改变。病理改变包括系膜区细胞数量增多，系膜基质扩张。此外，当我们在野生型和巨细胞蛋白转基因小鼠中诱导抗肾小球基底膜(GBM)肾炎时，只有转基因小鼠的系膜扩张持续存在。在巨蛋白转基因小鼠的肾小球病变中，伴随着免疫球蛋白和补体的增强的免疫复合体沉积。这些小鼠免疫复合体(IC)沉积的主要机制不太可能是产量增加，因为转基因小鼠的循环IC水平充其量是微不足道的。对这一现象的解释应该是系膜细胞清除免疫复合体等大分子的能力降低。我们推测，系膜优势基因Megsin的过度表达可能导致系膜功能障碍，损害IC的降解和处置，改变系膜基质的微环境。我们进行了半肾切除，以加速Megsin转基因小鼠的肾小球损伤。半肾切除转基因小鼠出现局灶性节段性系膜扩张，并伴有蛋白尿。该转基因小鼠半肾切除模型可作为研究肾小球疾病发病机制的工具。