PROTEIN-KINASE-C BETA(I) AND BETA(II) ARE DIFFERENTIALLY EXPRESSED IN THE DEVELOPING GLOMERULUS

In the pre- and postnatal period of kidney development, proliferation with subsequent functional maturation of intrinsic glomerular mesangial cells (MCs) continues within the existing framework. Recent work has suggested that PKC beta isoform is responsible for the proliferation observed during maturation. We sought to ascertain whether PKC beta isoform expression is altered during the development of the mesangium. MCs were subcultured from glomerular explants of Sprague-Dawley rat kidneys, days 1, 3, 5, 8, 15 postnatally, and adult. MCs from rat kidneys postnatally days 1-5 proliferated at a significantly greater rate than adult [>1.169-fold, P < 0.01] but term day 8 cells did not [<1.34-fold, not significant)] as assessed by [H-3]thymidine incorporation. Western blot analysis using isoform specific antibodies was performed on confluent neonatal and adult MC. We observed that all neonatal and adult MC express beta(I) PKC (n = 8 kidneys from separate primaries for each date and adult). However, unlike adult MCs, neonatal MC express beta(II) in postnatal days 1-5 and none thereafter. Immunofluorescent staining of postnatal kidneys confirmed that PKC beta(II) is present in neonatal MC up to day 5. By day 8, staining of mesangium with PKC beta(II) begins to disappear and assumes a parietal epithelial pattern. In adult kidneys, there was only PKC beta(II) staining of the parietal epithelial cells. Our results demonstrate that differential expression of PKC beta(II) closely parallels the proliferative behavior of the MCs of the maturing glomerulus. Therefore, PKC beta(II) expression and activation may play a critical role in development.