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Hormonal system for regulating local defense

调节局部防御的荷尔蒙系统

基本信息

批准号：
12460129
负责人：
KON Yasuhiro
金额：
$ 8.51万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

It has been known that hormones regulate several functions as a physiological ligand. Renin-angiotensin system (RAS)plays functions for regulating blood pressure and water-mineral balance. Renin produced mainly from kidney is thought to be also synthesized by other tissues, however, its real functions are under discussion. In the present study, the relationship between RAS and local immune defense were investigated by morphological and biochemical techniques. The morphological analysis of renin knockout mice suggested the following results. The kidneys of null mutant mice showing more or less hydronephrosis, possessed the characteristics of the endothelial hypertrophy and the proliferation of smooth muscle cells. Blood pressure was markedly decreased. Numerous nerve fibers were observed surrounding intrarenal vessel walls by PGP9.5-immunostaining. On the other hand, no morphological changes were detected in the extrarenal tissues, especially in the coagulating gland. These results suggested that renin is essential for renal morphogenesis, but is compensated in the extrarenal tissues by other unknown factors. The localization of inducible nitric oxide synthase(iNOS) was investigated in mouse testis in attention to immune defense. Interestingly, iNOS was detected in association to the distribution of blood-testis barrier, in which its immunoreactivity was changed according to seminiferous stages. Additionally, the analysis of meiotic metaphase-specific apoptosis in the testis of MRL strain was resulted that it was caused by the genetic mutation of Exonuclease 1. Finally, to investigate the potent function of oviduct glycoprotein, transgenic mice carrying its promoter and SV large T antigen genes were created, resulting that its expression was associated with tumorigenesis of thyroid gland.

众所周知，激素作为生理配体调节多种功能。肾素-血管紧张素系统（RAS）具有调节血压和水矿物质平衡的功能。人们认为主要由肾脏产生的肾素也可以由其他组织合成，然而，其真正功能仍在讨论中。在本研究中，通过形态学和生化技术研究了RAS与局部免疫防御之间的关系。肾素敲除小鼠的形态学分析表明了以下结果。无效突变小鼠的肾脏表现出或多或少的肾积水，具有内皮肥大和平滑肌细胞增殖的特征。血压明显下降。通过PGP9.5免疫染色观察到肾内血管壁周围有许多神经纤维。另一方面，在肾外组织，特别是凝固腺中没有检测到形态变化。这些结果表明肾素对于肾脏形态发生至关重要，但在肾外组织中被其他未知因素补偿。研究诱导型一氧化氮合酶（iNOS）在小鼠睾丸中的定位，以关注免疫防御。有趣的是，iNOS 的检测与血睾屏障的分布有关，其中其免疫反应性根据生精阶段而变化。另外，分析MRL品系睾丸减数分裂中期特异性细胞凋亡是由核酸外切酶1基因突变引起的。最后，为了研究输卵管糖蛋白的强大功能，创建了携带其启动子和SV大T抗原基因的转基因小鼠，结果发现其表达与甲状腺肿瘤发生有关。