ANGIOTENSIN IN CONTROL OF RENAL GROWTH

血管紧张素控制肾脏生长

• 批准号: 3235562
• 负责人: LEON G FINE
• 金额: $ 9.53万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3235562
• 关键词: angiotensin II; epidermal growth factor; growth /development; growth inhibitors; hormone regulation /control mechanism; kidney hyperplasia; kidney hypertrophy; phosphatidylinositols; prostaglandin E

Growth of the adult kidney may occur by hypertrophy (e.g. following reduction of renal mass) or hyperplasia (e.g. following acute tubular necrosis). The factors which control these different patterns are unknown. Furthermore, the existence of a kidney-specific growth factor has never been established with certainty. In the proposed studies we will examine the hypothesis that angiotensin II, which is generated locally within the kidney, is a growth factor for renal proximal tubular (PT) cells, but rather than acting like most growth factors to stimulate cell proliferation, it causes hypertrophy of the cell. We further postulate that the interactions of angiotensin II with two other molecules produced by the kidney i.e. epidermal growth factor (EGF) and growth inhibitor/transforming growth factor (GI/TGFBeta) determine whether hypertrophy or hyperplasia occur. According to this approach, moderate elevation of the local angiotensin II concentration would cause hypertrophy whereas more exaggerated increments would potentiate the effects of non-mitogenic concentrations of EGF to cause hyperplasia. These effects will be studied in vitro on primary cultures of PT cells as will the role of GI/TGFBeta production in determining the pattern of the growth response. The mechanism of action of angiotensin II will be studied by examining its effects on membrane phosphoinositide turnover, prostaglandin E2 synthesis and Na/H antiport. The causal role of the latter two processes in hypertrophy will be evaluated by selective blockade during prolonged exposure to angiotensin II.

成人肾脏的生长可通过肥大发生（例如， 肾质量减少）或增生（例如，急性肾小管 坏死）。 控制这些不同模式的因素是 未知 此外，肾特异性生长因子的存在 从未被确定过。 在拟议的研究中，我们将 研究血管紧张素II，这是局部产生的假设， 是肾近端小管（PT）的生长因子， 细胞，而不是像大多数生长因子一样刺激细胞生长， 增殖，它会导致细胞肥大。 我们进一步假设 血管紧张素II与其他两种分子的相互作用 表皮生长因子（EGF）和生长因子 抑制剂/转化生长因子（GI/TGF β）测定是否 发生肥大或增生。 根据这一方针， 局部血管紧张素II浓度升高会导致肥大 而更夸张的增量将增强 非促有丝分裂浓度的EGF导致增生。 这些影响 将在PT细胞的原代培养物上进行体外研究， GI/TGF β的产生在决定生长反应的模式。 血管紧张素II的作用机制将通过检查其 对膜磷脂酰肌醇转换、前列腺素E2合成的影响 和Na/H反向转运。 后两个过程的因果作用， 将通过选择性阻断来评价肥大， 暴露于血管紧张素II。