IMMUNE AND NONIMMUNE BASES OF RENAL DISEASE

在过去的15年里，私家侦探努力调查 而肾脏疾病的非免疫机制已逐渐集中在 肾素-血管紧张素系统(RAS)的作用通过动物和人体研究， PT已经证明血管紧张素II会对肾脏造成损害 通过几种以前认识到的和未认识到的生物特性。 试图找出与这一事件有关的特定生物事件 血管紧张素II的作用，PI迈出了完全和选择性的一步 使组成RAS的几个基因失活，即其前体的基因， 代谢酶和受体。 然而，从分析产生的突变体的早期阶段开始，PI开始 要认识到RAS在人的个体发育中具有重要的生理作用 肾脏和尿路，事实上，这一系统的缺陷会导致 肾脏和尿路疾病。其中一个基因的突变会导致 甚至与一组常见的(1/100出生)先天人类有关 疾病，统称为“先天性肾脏异常”和 尿路。利用这个新到来的机会，PI现在计划 描述这一疾病实体的个体发生，同时， RAS在正常肾脏和尿路中的生理作用 发展。

Over the last 15 years, the PI's effort to investigate the 'immune and non-immune mechanisms of renal diseases' has progressively focused on the role of the renin-angiotensin system (RAS). Through animal and human studies, the PT has documented that angiotensin II produces damages to the kidney through several previously recognized and unrecognized biological properties. In an attempt to pinpoint the specific biological events involved in the actions of angiotensin II, the PI took the step to completely and selectively inactivate the several genes comprising RAS, i.e., the genes of its precursor, metabolizing enzyme and receptors. From the early stage of analyzing the produced mutants, however, the PI began to realize that RAS has an important physiological role for the ontogeny of the kidney and urinary tract, and that, in fact, a defect in this system, can cause diseases of the kidney and urinary tract. A mutation in one of those genes has even been linked to a special group of common (1 / 100 births) congenital human diseases, which are collectively called 'congenital anomalies of the kidney and urinary tract'. Taking this newly arrived opportunity, the PI now plans to delineate the ontogeny of this disease entity, and at the same time, to shed light into the physiologic role of RAS in normal kidney and urinary tract development.