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.

临床和实验中的许多增殖性肾小球病 设置有一个共同点，即血小板激活、分泌和 在治疗过程中血小板产物的肾小球定位 疾病过程。建议进行研究以批判性地审查 血小板分泌蛋白（PSP）对增殖的影响 增殖性肾小球病加速模型中的系膜细胞 其中，系膜增殖是由哈布蛇毒（HSV）诱导的。 血小板α颗粒蛋白（血小板衍生生长 因子-[PDGF]、转化生长因子α和β[TGF-α、 TGF-β] 血小板因子 4 (PF4) 表皮生长因子 (EGF) 和 血小板纤连蛋白 (Fn) 在系膜增殖发展中的作用 将通过监测 PSP 分泌、肾小球定位来检查 PSP，以及细胞定位和增殖。 PSP的特殊性 肾小球增殖的参与将通过确定来评估 除血小板外参与的细胞的贡献 PDGF、TGF-α和TGF-β的mRNA的合成和表达以及 他们翻译的蛋白质。针对特定 PSP 或 受体将用于中和和干扰 PSP 系膜 细胞相互作用并调节增殖性病变。 PDGF、TGF-α、 TGF-β、PF4 和血小板 Fn 将被验证为生长因子 体内通过重现导致增殖的事件序列 将血小板输注回接受 HSV 治疗的大鼠的肾脏中 已被抗血小板血清耗尽。研究将检查具体 作用机制（迁移、有丝分裂和中和） 生长抑制物质（肝素）通过培养物中的特定 PSP 进行。这些 研究将提供有关 PSP 系膜的有价值的信息 进行性、增殖性肾小球肾炎中的相互作用。