Glomerular basement membrane permeability factor in minimal change nephrotic syndrome

微小病变肾病综合征的肾小球基底膜通透性因子

• 批准号: 02670440
• 负责人: YOSHIKAWA Norishige
• 金额: $ 1.34万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670440/
• 关键词: minimal change nephrotic syndrome; glomerular basement membrane permeability; proteinuria; peripheral blood mononuclear cell; anionic sites; vascular permeability factor; Northern blot analysis; mesangial cells; リンバ球

Minimal change nephrotic syndrome(MCNS)is the most common form of nephrotic syndrome in children. However, the pathogenesis of MCNS remains unknown. Several investigators have been proposed suggesting that MCNS is immune-mediated disorder. Shalhoub postulated that lymphocytes in patients with MCNS produce a lymphokine that causes increased permeability of the glomerular basement membrane(GBM), resulting in proteinuria and nephrotic syndrome.Supernatants of peripheral blood mononuclear cell culture from children with MCNS were tested for their ability to increase GBM permeability and for effects on anionic sites in the GBM. Supernatants from cultures of concanavalin A-stimulated peripheral blood mononuclear cells from patients with MCNS were infused into the renal arteries of normal rats. Infusion caused a significant reduction of anionic sites in the GBM and a significant increase in urinary albumin excretion. These findings show that stimulation of peripheral blood mononuclear cells from MCNS results in liberation of soluble substances which reduce polyanions in the GBM and increase GBM permeability.Recently vascular permeability factor(VPF)has been purified from human lymphoma line. VPF increases fluid permeability from blood vessels. Northern blot analysis revealed that human peripheral blood mononuclear cells and glomerular mesangial cells expressed VPF mRNA. VPF protein was also detected in human mesangial cells. VPF infusion into rats resulted in a dosedependent increase in urinary albumin excretion. These findings indicate that mesangial cells and peripheral blood mononuclear cells produce VPF and VPF released from these cells induces albuminuria in MCNS.

微小病变型肾病综合征(MCNS)是儿童最常见的肾病综合征。然而，MCNS的发病机制仍不清楚。一些研究人员提出，MCNS是一种免疫介导的疾病。Shalhoub推测，MCNS患者的淋巴细胞产生一种淋巴因子，导致肾小球基底膜(GBM)通透性增加，导致蛋白尿和肾病综合征。测试了MCNS儿童外周血单个核细胞培养上清液增加GBM通透性的能力以及对GBM阴离子部位的影响。将刀豆蛋白A刺激的MCNS患者外周血单个核细胞培养上清注入正常大鼠肾动脉。输液后基底膜阴离子位置显著减少，尿白蛋白排泄量显著增加。这些结果表明，刺激外周血单核细胞可以释放出可溶性物质，从而减少GBM中的聚阴离子，增加GBM的通透性。最近，从人淋巴瘤细胞系中分离到了血管通透性因子(VPF)。VPF增加了来自血管的液体渗透率。Northern印迹分析表明，人外周血单个核细胞和肾小球系膜细胞表达VPF基因。在人肾小球系膜细胞中也检测到VPF蛋白。大鼠输注VPF后，尿白蛋白排泄量呈剂量依赖性增加。这些发现表明，系膜细胞和外周血单核细胞产生VPF，从这些细胞释放的VPF在MCNS诱导蛋白尿。

项目成果

Iijima K, Yoshikawa N, Connolly DT, Nakamura H: "Human mesangial cells and peripheral blood mononuclear cells produce vascular permeability factor." Kidney Int.In submission. (1993)

Iijima K、Yoshikawa N、Connolly DT、Nakamura H：“人类系膜细胞和外周血单核细胞产生血管通透性因子。”

K.KOKUI: "Cyclosporin reduces proteinuria in rats with aminonucleoside nephrosis." J.Pathol. 166. 297-301 (1992)

K.KOKUI：“环孢素可降低氨基核苷肾病大鼠的蛋白尿。”

Tanaka R, Yoshikawa N, Nakamura H, Ito H: "Infusion of peripheral blood mononuclear cell products from nephrotic children increases albuminuria in rats." Nephron. 60. 35-41 (1992)

Tanaka R、Yoshikawa N、Nakamura H、Ito H：“输注肾病儿童的外周血单核细胞产物会增加大鼠的蛋白尿。”