ROLE OF POLYCATIONIC MEDIATORS IN GLOMERULONEPHRITIS

临床和实验中的一些增生性肾小球疾病 设置有一个共同的，发作的血小板激活，分泌，和 肾小球内血小板产物在肾小球中的定位 疾病过程。建议进行研究，以批判性地检查 血小板分泌蛋白(PSP)对血管内皮细胞增殖的影响 系膜细胞在增殖性肾小球疾病加速模型中的作用 其中，哈布蛇毒(HSV)可诱导系膜细胞增殖。 血小板α颗粒蛋白(血小板源生长)的影响 转化生长因子α和β[转化生长因子-α， 血小板因子4(PF4)、表皮生长因子(EGF)和 血小板纤维连接蛋白(FN)在系膜细胞增殖中的作用 将通过监测PSP分泌、肾小球定位进行检查 PSP、细胞定位和增殖。PSP的特异性 对肾小球增殖的参与程度将通过以下方式进行评估 除血小板外的其他细胞参与的作用 血小板衍生生长因子、转化生长因子-α和转化生长因子-β基因的合成及表达 它们的翻译蛋白质。针对特定PSP或 受体将被用来中和和干扰PSP-系膜 细胞相互作用和调节增殖性病变。PDGF、转化生长因子-α、 转化生长因子-β、PF4和血小板FN将被证实为 通过再现导致增殖的一系列事件而活着 回输给HSV治疗的大鼠的肾脏，其中血小板有 已经被抗血小板血清消耗殆尽。研究将检查特定的 作用机制(迁移、有丝分裂和中和 生长抑制物质，肝素)在培养中的特异性PSP。这些 研究将提供有关PSP-系膜的宝贵信息 进行性、增生性肾小球肾炎的相互作用。

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.