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Study on a possible function of tenascin-C in wound healing of glomerulonephritis

Tenascin-C 在肾小球肾炎伤口愈合中的可能作用研究

基本信息

批准号：
09671187
负责人：
KUSAKABE Moriaki
金额：
$ 2.05万
依托单位：
The Institute of Physical and Chemical Research (RIKEN)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Mice without the gene for tenascin-C, a multifunctional extracellular matrix protein expressed in many important biological events, including wound healing, did not show any phenotype. However, it is now obvious that the phenotype of deletion of one gene frequently depends on the genetic background. Therefore, we have newly generated tenascin-C knockout mice(KO)by backcrossing original KO into three congenic lines : C57BL/6N, BALB/cA, and GRS/A (GR). And we investigated the disease course of reversible kidney injury, Habu-snake venom-induced proliferative glomerulonephritis. In all strains, the disease was more severe in KO, but the severity varied with the strain. The KO-GR showed abnormal regenerative reactions, including reduced proliferation of mesangial cells, key players in glomerulonephritis, and reduced production of some kinds of cytokines and matrices, leading to poor formation of granulation tissue. In culture, the mesangial cells from the KO-GR had the same potential for proliferation and response to cytokines as controls, but interestingly, to achieve this potential, they required contact with tenascin-C.These reactions were blocked by an anti-tenascin monoclonal antibody. The results of the present study, the first report showing the most dramatic phenotype so far discovered, have strongly suggested the importance of tenascin-C in the resolution of the renal inflammation and that of the genetic background on which the KO was developed.

没有腱生蛋白-C基因的小鼠没有表现出任何表型，腱生蛋白-C是一种多功能细胞外基质蛋白，在许多重要的生物学事件中表达，包括伤口愈合。然而，现在很明显，一个基因缺失的表型通常取决于遗传背景。因此，我们通过将原始KO回交到三个同源系：C57 BL/6 N、BALB/cA和GRS/A（GR）中，新产生了腱生蛋白-C敲除小鼠（KO）。并对可逆性肾损伤--河豚蛇毒致增生性肾小球肾炎的病程进行了观察。在所有菌株中，疾病在KO中更严重，但严重程度因菌株而异。KO-GR表现出异常的再生反应，包括肾小球肾炎中的关键参与者系膜细胞增殖减少，以及某些细胞因子和基质的产生减少，导致肉芽组织形成不良。在培养中，来自KO-GR的系膜细胞具有与对照相同的增殖和对细胞因子的反应潜力，但有趣的是，为了实现这种潜力，它们需要与腱生蛋白-C接触。这些反应被抗腱生蛋白单克隆抗体阻断。本研究的结果是迄今发现的最引人注目的表型的第一份报告，强烈表明了腱生蛋白-C在解决肾脏炎症和KO发展的遗传背景中的重要性。