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Molecular architecture and gene expression of glomerular extracellular matrix.

肾小球细胞外基质的分子结构和基因表达。

基本信息

批准号：
04404039
负责人：
OTA Zensuke
金额：
$ 14.08万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04404039/
关键词：
kidney glomerular basement membrane ultrafine structure electron microscope extracellular matrix integrin gene mesangium 基底膜ネフローゼ症候群接着分子タンパク尿 Tissue negative staining ネフローゼトンネル糖尿病性腎炎 Tissue Negative Staining コラーゲン

项目摘要

We observed the normal kidneys and kidneys of diabetic nephropathy and membranous nephropathy patients showing nephrotic syndrome by newly devised "tissue negative staining method" established by Z.Ota, principal investigator. In normal kidneys, glomerular basement membrane (GBM) showed fine meshwork structure consisted of fibrils, and pore size was 2-3nm. In nephrotic patients, pore size was increased and tunnel-like structures (named nephrotic tunnel) with 20-100 nm diameter, which penetrate GBMs from capillary lumen to urinaru lumen. The diameter of this nephrotic tunnel is larger than the albumin molecules, and thus this structure is tightly related to the etiology of the nephrotic syndrome.By ultra-high resolution scanning electron microscopy, we observed the isolated GBM and glomeruli treated with detergent. Furthermore, we investigated the components of the GBMs, by immunoelectron microscopy using the specific antibodies against type IV collagen, hepara sulfate proteoglycans and fibronectins. The GBM was mainly consisted of type IV collagens and three dimentional meshwork.In various forms of glomerulonephritis, the expression of integrins were investigated by immunohistochemistry. In IgA nephropathy, membranous proliferative glomerulonephritis, and lupus nephritis, beta1 integrins and alphav-related receptors were upregulated in the glomeruli. The ligands of integrins, i.e.finronectin, vitronectin and type IV collagens were also increased in the glomeurli. These results indicated that integrin may be involved in the progression of mesangial proliferative glomerulonephritis.

本研究采用Ota先生新发明的“组织负染法”对正常肾脏和糖尿病肾病及膜性肾病肾病患者的肾脏进行了观察。正常肾脏肾小球基底膜（GBM）呈细纤维网状结构，孔径2- 3 nm。在肾病患者中，孔径增大，并形成直径为20-100 nm的隧道样结构（称为肾病隧道），其从毛细血管腔到尿腔穿透GBM。本实验通过超高分辨扫描电镜观察了经洗涤剂处理的肾小球基底膜和肾小球，并对肾小球基底膜的超微结构进行了观察。此外，我们研究了GBM的组成部分，通过免疫电镜使用针对IV型胶原，硫酸乙酰肝素蛋白多糖和纤维连接蛋白的特异性抗体。肾小球基底膜主要由IV型胶原和三维网状结构组成，免疫组化法检测了整合素在各种类型肾小球肾炎中的表达。在伊加肾病、膜性增生性肾小球肾炎和狼疮性肾炎中，肾小球中β 1整合素和α v相关受体上调。整合素的配体，即finronectin、vitronectin和IV型胶原在肾小球中也增加。提示整合素可能参与了系膜增生性肾小球肾炎的发生、发展过程。