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Mechanisms of sclerosis in the glomerulus as a representative of microcirculation

作为微循环代表的肾小球硬化机制

基本信息

批准号：
04670199
负责人：
OITE Takashi
金额：
$ 0.26万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

With aid of the above grant, we have researched and reported on the mechanisums of glomerulosclerosis. We have obtained the following results during the period of research project :(1) When human mesangial cells(HMC) were cultured on a reconstituted basement membrane, Matrigel HMC aggregated and formed isolated colonies, then extended an array of cell processes to form a dendritic network structure and proliferated very slowly. On type I collagen gel, HMC showed rapid cell growth.(2) Mesangial cell proliferation was inhibited markedly on gels containing type III collagen, heparin and heparan sulphate ; type IV collagen suppressed HMC proliferation.(3) Conditioned medium(CM) of cultured mesangial cells showed the inhibitory activity on mesangial cell proliferation, which was absorbed with anti-TGF-beta antibody. In CM, less than 10% of TGF-beta was present in active form. Direct addition of anti-TGF-beta antibody to culture media enhanced mesangial cell proliferation.(4) The effect of direct cell contact between endothelial and mesangial cells on mesangial cell behavior was examined in a coculture system. MoAb.1-22-3 was bound preferentially to the limited mesangial cell surface facing endothelial cells.(5) There is a difference in reactivity between MoAb.1-22-3 and anti-Thy1.1 Ab(OX-7).Now, we are investigating a new epitope detected with MoAb.1-22-3 at the cellular (immune electronmicroscopic) and molecular (using cDNA for Thy-1 gene) levels.

在上述资助的帮助下，我们对肾小球硬化的机制进行了研究和报道。(1)人肾小球系膜细胞(HMC)在重组基底膜上培养时，Matrigel HMC聚集并形成孤立的集落，然后延伸细胞突起形成树突状网络结构，增殖非常缓慢。在I型胶原凝胶上，系膜细胞生长迅速。(2)在含有III型胶原、肝素和硫酸肝素的凝胶上，系膜细胞的增殖受到明显抑制；在IV型胶原凝胶上，系膜细胞的增殖受到抑制。(3)系膜细胞的条件培养液(CM)对系膜细胞的增殖有抑制作用，并被抗转化生长因子-β抗体所吸收。在CM中，只有不到10%的转化生长因子-β以活性形式存在。直接加入抗转化生长因子-β抗体可促进系膜细胞增殖。(4)在共培养体系中观察内皮细胞与系膜细胞直接接触对系膜细胞行为的影响。(5)MoAb.1-22-3与抗Thy1.1抗体(OX-7)的反应性存在差异。现在，我们正在研究MoAb.1-22-3在细胞(免疫电子显微镜)和分子(利用Thy-1基因的基因)水平上检测到的一个新的表位。