ROLE OF POLYCATIONIC MEDIATORS IN GLOMERULONEPHRITIS

聚阳离子介质在肾小球肾炎中的作用

• 批准号: 3238230
• 负责人: JEFFREY L BARNES
• 金额: $ 11.85万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3238230
• 关键词: autoimmune disorder; binding proteins; blood cell depletion therapy; cell migration; cellular immunity; dipyridamole; epidermal growth factor; fibronectins; gene expression; glomerulonephritis; immunocytochemistry; immunofluorescence technique; in situ hybridization; inflammation; kidney disorder chemotherapy; kidney pharmacology; laboratory rat; messenger RNA; neutralizing antibody; neutrophil; northern blottings; nucleic acid probes; nucleic acid sequence; platelet activation; platelet derived growth factor; prostacyclins; reptile poison; secretory protein; tissue /cell culture; transforming growth factors

A number of proliferative glomerulopathies in clinical and experimental settings have a common, episodes of platelet activation, secretion, and glomerular localization of platelet products during the course of the disease processes. Studies are proposed to critically examine the influence of platelet secretory proteins (PSP) on proliferation of mesangial cells in an accelerated model of proliferative glomerulopathy in which mesangial proliferation is induced by Habu snake venom (HSV). Influences of platelet alpha granule proteins (platelet derived growth factor -[PDGF], transforming growth factors alpha and beta [TGF-alpha, TGF-beta] platelet factor 4 (PF4) epidermal growth factor (EGF) and platelet fibronectin (Fn) in the development of mesangial proliferation will be examined by monitoring PSP secretion, glomerular localization of PSP, and cell localization and proliferation. The specificity of PSP involvement in glomerular proliferation will be evaluated by determining the contribution of cells other than platelets that are involved in synthesis and expression of MRNA for PDGF, TGF-alpha and TGF-beta and their translated proteins. Antibodies raised against specific PSP or receptors will be used to neutralize and interfere with PSP-mesangial cell interaction and modulate proliferative lesions. PDGF, TGF-alpha, TGF-beta, PF4, and platelet Fn will be verified as growth factors in vivo by recreation of the sequence of events leading to proliferative by infusion back into kidneys of HSV-treated rats, in which platelets have been depleted by anti-platelet serum. Studies will examine specific mechanisms of action (migration, mitogenesis and neutralization of a growth inhibiting substance, heparin) by specific PSP in culture. These studies will provide valuable information regarding PSP-mesangial interactions in progressive, proliferative glomerulonephritis.

临床和实验性的许多增生性肾小球病 设置有一个常见的血小板激活，分泌的情节和 血小板产物的肾小球定位 疾病过程。提出了研究以批判性检查 血小板分泌蛋白（PSP）对增殖的影响 在增生性肾小球病模型的加速模型中的肾小球细胞 HABU蛇毒（HSV）诱导了肾小球增殖。 血小板α颗粒蛋白的影响（血小板衍生生长 因子 - [PDGF]，转化生长因子alpha和beta [tgf -alpha， TGF-β]血小板因子4（PF4）表皮生长因子（EGF）和 肾小球增殖发展中的血小板纤连蛋白（FN） 将通过监视PSP分泌，肾小球定位来检查 PSP以及细胞定位和增殖。 PSP的特异性 通过确定，将评估参与肾小球增殖 涉及的血小板以外的细胞的贡献 PDGF，TGF-ALPHA和TGF-BETA的MRNA的合成和表达 他们翻译的蛋白质。针对特定PSP或 受体将被用来中和并干扰PSP-膜状 细胞相互作用并调节增殖性病变。 PDGF，TGF-Alpha， TGF-β，PF4和血小板FN将被验证为生长因子 体内通过娱乐事件的序列，导致逐渐增殖 输液回到了经HSV处理的大鼠的肾脏中，血小板有 被抗血清血清耗尽。研究将研究特定 作用机制（迁移，有丝分裂和中和 培养中特定PSP的生长抑制物质，肝素）。这些 研究将提供有关PSP膜的有价值的信息 进行性增殖性肾小球肾炎中的相互作用。