The roles of vascular permeability factor/vascular endothelial growth factor in mesangial proliferative glomerulonephritis

血管通透因子/血管内皮生长因子在系膜增生性肾小球肾炎中的作用

• 批准号: 08671286
• 负责人: IIJIMA Kazumoto
• 金额: $ 1.41万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671286/
• 关键词: Vascular permeability factor; Vascular endothelial growth factor; Renal biopsy specimen; Mesangial cells; alpha-smooth muscle actin; Mesangial proliferative glomerulonephritis; α-Smooth muscle achin; 腎生検組織; α-smooth muscle actin

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine involved in angiogenesis, inflammation and wound healing. VPF/VEGF has been reported to be produced only by glomerular podocytes in glomeruli and we found that it si produced by human cultured mesangial cells (MC). Therefore, we performed immunohistochemical analysis, using indirect immunofluorescence and in situ hybridization, of VPF/VEGF in normal kidneys (n=7) and biopsy specimens taken from 83 patients with renal diseases, including mesangial proliferative glomerulonephritis (PGN,n=58), to examine whether VPF/VEGF is produced by MC in human PGN.In all the normal subjects and all the patients except those with PGN (disease controls), VPF/VEGF protein and mRNA were detected mainly in podocytes, indicating that VPF/VEGF was produced mainly by podocytes. However, in some PGN patients, VPF/VEGF protein was demonstrated clearly in MC as well as in podocytes, as some … More of the VPF/VEGF was co-localized with alpha-smooth muscle actin, a marker of activated MC,and VPF/VEGF mRNA was expressed by MC and podocytes. Mesangial VPF/VEGF expression in PGN patients with early lesions (predominant mesangial hypercellularity) was enhanced significantly compared with that in those with later lesions (similar degree of mesangial hypercellularity and increased matrix, p<0.01, or predominant mesangial matrix increase, p<0.05), that in disease controls and normal subjects (both p<0.01). The time between biopsy and disease onset was significantly shorter in PGN patients with than without mesangial VPF/VEGF expression (p<0.01). These findings provide the first evidence that activated MC are a source of VPF/VEGF in human PGN,and indicate that mesamgial VPF/VEGF expression is characteristic of early lesions of PGN.As VPF/VEGF plays a pivotal role in tissue repair, MC-produced VPF/VEGF may play pathophysiological roles, including promoting recovery from glomerular injuries, in early-stage PGN. Less

血管通透性因子(VPF)又称血管内皮生长因子(VEGF)，是一种多功能细胞因子，参与血管生成、炎症反应和创面愈合。VPF/VEGF仅由肾小球中的足细胞产生，我们发现它是由培养的人肾小球系膜细胞产生的。因此，我们用间接免疫荧光和原位杂交的方法，对正常肾组织(n=7)和包括系膜增生性肾小球肾炎(n=58)在内的83例肾脏疾病患者的肾活检标本进行了VPF/VEGF的免疫组织化学分析，以了解肾小球系膜增生性肾炎(PGN)患者肾组织中VPF/VEGF的表达是否由肾小球系膜细胞产生。然而，在一些PGN患者中，vpf/VEGF2蛋白在MC和足细胞中都有明显的表达，在一些…中也有表达。VPF/VEGF多与活化MC的标志物α-平滑肌肌动蛋白共定位，VPF/VEGFmRNA主要由MC和足细胞表达。与疾病对照组和正常对照组相比，早期病变(以系膜细胞增多为主)的PGN患者系膜VPF/VEGF表达显著增强(P<0.01)。肾小球系膜血管内皮生长因子/血管内皮生长因子表达阳性的肾小球肾炎患者从活检到发病的时间明显缩短(p&lt；0.01)。这些发现首次提供了激活的MC是人PGN中VPF/VEGF的来源的证据，并表明系膜VPF/VEGF的表达是PGN早期病变的特征。由于VPF/VEGF在组织修复中起关键作用，MC产生的VPF/VEGF可能在早期PGN中发挥病理生理作用，包括促进肾小球损伤的恢复。较少

项目成果

Iijima K.: "Childhood IgA nephropathy : the mechanisms of progression and a new effective therapy (Japanese)" The Journal of the Japan Pediatric Society. 100. 1445-1448 (1996)

Iijima K.：“儿童 IgA 肾病：进展机制和新的有效疗法（日语）”日本儿科学会杂志。

飯島 一誠 他: "活性化メサンギウム細胞による血管透過性亢進因子(VPF/VEGF)の産生とその病態生理学的意義" 日本小児腎臓病学会雑誌. 10(1). 22-25 (1997)

Kazumasa Iijima 等人：“活化的系膜细胞产生血管通透性增强因子 (VPF/VEGF) 及其病理生理学意义”，日本小儿肾脏病学会杂志 10(1) (1997)。

飯島一誠他: "活性化メサンギウム細胞による血管透過性亢進因子(VPF/VEGF)の産生とその病態生理学的意義" 日本小児腎臓病学会雑誌. 10(1). 22-25 (1997)

Kazumasa Iijima 等人：“活化的系膜细胞产生血管通透性增强因子 (VPF/VEGF) 及其病理生理学意义”，日本小儿肾脏病学会杂志 10(1) (1997)。

Iijima K et al.: "Activation-induced expression of vascular permeability factor by human peripheral T cells a non-radioisotopic semiquantitative reverse transcription-polymerase chain reaction assay." Journal of Immunological Methods. 196. 199-209 (1996)

Iijima K 等人：“人外周 T 细胞激活诱导表达血管通透性因子，一种非放射性同位素半定量逆转录聚合酶链反应测定。”

Iijima K et al.: "Activation-induced expression of vascular permeability factor by human peripheral T cells:a non-radioisotopic semiquantitative reverse transcription-polymerase chain reaction assay" Journal of Immunological Methods. 196. 199-209 (1996)

Iijima K 等人：“人外周 T 细胞激活诱导的血管通透因子表达：非放射性同位素半定量逆转录聚合酶链反应测定”《免疫学方法杂志》。