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

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，荷尔蒙作为一种生理配体调节多种功能。肾素-血管紧张素系统(RAS)起着调节血压和水矿平衡的作用。肾素主要由肾脏产生，也可由其他组织合成，然而，其真正的功能仍在讨论中。本研究用形态和生化技术研究了RAS与局部免疫防御的关系。肾素基因敲除小鼠的形态分析结果如下。缺失型突变小鼠肾脏表现为不同程度的肾积水，表现为血管内皮细胞肥大和平滑肌细胞增殖。血压明显下降。PGP9.5免疫组织化学染色显示肾内血管壁周围可见大量神经纤维。肾外组织，尤其是凝固腺未见明显的形态变化。这些结果表明，肾素在肾脏形态发生中是必需的，但在肾外组织中被其他未知因素所补偿。为了研究免疫防御，对诱导型一氧化氮合酶(INOS)在小鼠睾丸中的定位进行了研究。有趣的是，iNOS的检测与血-睾丸屏障的分布有关，在血-睾丸屏障中，其免疫反应性随生精阶段的不同而变化。此外，对MRL株的减数分裂中期特异性细胞凋亡进行了分析，结果表明它是由外切酶1的基因突变引起的。最后，为了研究输卵管糖蛋白的潜在功能，建立了携带其启动子和SV大T抗原基因的转基因小鼠，结果表明其表达与甲状腺肿瘤的发生有关。