Vascular endothelial growth factor mRNA expression in minimal change, membranous, and diabetic nephropathy demonstrated by non-isotopic in situ hybridisation

Aim-To investigate vascular endothelial growth factor (VEGF) mRNA expressio n: in glomerular disease in the context of heavy proteinuria. Methods-Non-radioisotopic in situ hybridisation was performed using a cockt ail of 12 deoxyoligonucleotides complementary to VEGF mRNA labelled during solid phase synthesis with 2,4-dinitrophenyl. Archival renal biopsies were studied from cases of minimal change nephropathy, membranous nephropathy, d iabetic nephropathy, and controls, matched for age, sex, race, and storage time. Hybrid detection used NBT/BCIP colorimetric development. Results-More VEGF mRNA positive glomerular cells per unit cross sectional d iameter were seen in minimal change nephropathy (mean (SEM), 19.35 (1.5)) c ompared with controls (12.6 (1.73)) p < 0.01. In contrast, fewer were seen in diabetic nephropathy (5.93 (0.97)) compared with controls (9.97 (1.25)), p < 0.03. Analysis of membranous nephropathy (10 (1.62)) showed no differe nce from controls (10.98 (1.51)), NS. In addition, in minimal change nephro pathy there was a significant correlation between 24 hour protein excretion at the time of biopsy and the number of VEGF mRNA cells per glomerulus (r = 0.08, p = 0.01). Conclusions-Using non-radioisotopic in situ hybridisation, VEGF mRNA is alm ost exclusively expressed by visceral glomerular epithelial cells. Abnormal numbers of cells are seen in both minimal change and diabetic nephropathy. As VEGF exists in a number of functionally distinct isoforms, further stud y of qualitative VEGF isoform expression in diagnostic groups is indicated.