POLYCATIONIC MEDIATORS AND GLOMERULONEPHRITIS

多阳离子介质和肾小球肾炎

• 批准号: 2140643
• 负责人: JEFFREY L BARNES
• 金额: $ 11.97万
• 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/2140643
• 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.

在临床和实验室研究中， 设置有一个共同的，血小板活化，分泌， 血小板产物的肾小球定位过程中， 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）对人肝癌细胞增殖的影响 增生性肾小球病加速模型中的系膜细胞 其中系膜增殖由Habu蛇毒（HSV）诱导。 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（PF 4）表皮生长因子（EGF）和 血小板纤维连接蛋白（Fn）在系膜增生中的作用 将通过监测PSP分泌、肾小球定位、 PSP和细胞定位和增殖。PSP的特异性 肾小球增殖的参与将通过确定 除了血小板以外的细胞参与了 PDGF、TGF-α和TGF-β mRNA合成和表达， 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、PF 4和血小板Fn将被验证为生长因子， 通过重建导致增殖的事件序列， 输注回HSV处理的大鼠的肾脏，其中血小板具有 已经被抗血小板血清耗尽了研究将检查具体的 作用机制（迁移、有丝分裂和中和 生长抑制物质，肝素）。这些 研究将提供关于PSP系膜的有价值的信息 进行性增生性肾小球肾炎的相互作用。