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

血管通透性因子（Vascular permeability factor， VPF）又称血管内皮生长因子（Vascular endothelial growth factor， VEGF），是一种参与血管生成、炎症和伤口愈合的多功能细胞因子。据报道，VPF/VEGF仅由肾小球足细胞产生，我们发现它是由人培养的系膜细胞（MC）产生的。因此，我们采用间接免疫荧光和原位杂交对正常肾脏（n=7）和83例肾脏疾病（包括系膜增生性肾小球肾炎（PGN,n=58））的活检标本进行了免疫组织化学分析，以检测VPF/VEGF是否由MC在人PGN中产生。在所有正常受试者和除PGN（疾病对照）外的所有患者中，VPF/VEGF蛋白和mRNA主要在足细胞中检测到，说明VPF/VEGF主要由足细胞产生。然而，在一些PGN患者中，VPF/VEGF蛋白在MC和足细胞中都有明显的表达。VPF/VEGF更多地与α -平滑肌肌动蛋白（MC活化的标志）共定位，VPF/VEGF mRNA在MC和足细胞中表达。PGN早期病变患者系膜VPF/VEGF的表达明显高于晚期病变患者（系膜细胞增多程度相近，基质增多，p<0.01，或系膜基质增多，p<0.05）、疾病对照组和正常组（均p<0.01）。VPF/VEGF表达的PGN患者从活检到发病的时间明显短于未表达VPF/VEGF的PGN患者（p<0.01）。这些发现首次证明了活化的MC是人类PGN中VPF/VEGF的来源，并表明VPF/VEGF的系膜表达是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。少

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