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

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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