Vascular endothelial growth factor (VEGF-C1)-dependent inflammatory response of podocytes in nephrotic syndrome glomerulopathies in children: an immunohistochemical approach

AIMS: To analyse expression and distribution of vascular endothelial growth factor (VEGF-C1), podocalyxin and synaptopodin within renal tissue in nephrotic syndrome glomerulopathies in children. METHODS AND RESULTS: Renal biopsies performed at the time and in the manner recommended by the World Health Organization. The study group consisted of submicroscopic glomerulonephritis (n = 10), diffuse mesangial proliferation (n = 14) and focal segmental glomerulosclerosis (n = 5). The control tissue consisted of macroscopically normal appearing cortex taken from kidneys resected for localized neoplasms (n = 3). Material for immunohistochemistry was fixed in Bouin's solution and embedded in paraffin. Indirect immunohistochemistry using monoclonal anti-human antibodies directed against VEGF-C1, podocalyxin and synaptopodin was employed. The distribution of markers was quantified by computerized image analysis. In non-sclerosed glomeruli (within podocyte cytoplasm), VEGF-C1 was more expressed in podocytes of all groups (P < 0.0002), while the distribution of synaptopodin was less expressed in all groups (P < 0.0002). There was no statistical difference between all groups in the expression of podocalyxin. CONCLUSIONS: The increased permeability of the filtration barrier in steroid-resistant glomerulopathies may be a consequence of subcellular changes in podocytes resulting from decreased expression of synaptopodin. Moreover, impaired permeability of endothelium could be secondary to increased expression of podocyte-derived VEGF-C1.