ALTERATIONS IN THE EXPRESSION OF THE ALPHA(3)BETA(1) INTEGRIN IN CERTAIN MEMBRANE DOMAINS OF THE GLOMERULAR EPITHELIAL-CELLS (PODOCYTES) INDIABETES-MELLITUS

In view of the major alterations which take place at the level of the extracellular matrix of the glomerular wall in diabetes mellitus and t he key roles played by beta(1) integrins in cell-to-matrix interaction s, it is imperative to understand the role played by integrins in the development of diabetic glomerulosclerosis. In the present study, we r evealed by immunocytochemistry the ultrastructural distribution of the alpha(3) beta(1) at the level of the plasma membrane of the different renal glomerular cells from short- and long-term diabetic rats. For t he endothelial cells, the labelling present on both the luminal and ab luminal plasma membranes was low. For the podocyte epithelial cells, t he labelling was present on both the luminal and basal plasma membrane s, the former being concentrated at points of contact between podocyte foot processes. The labelling on the basal plasma membrane was more s ignificant and similar in domains facing either the glomerular basemen t membrane or the mesangial matrix. The plasma membrane of mesangial c ells also exhibited alpha(3) beta(1). The labelling was recorded under diabetic conditions, at the same sites, with similar intensities, alo ngside that of the basal plasma membrane of podocytes facing the glome rular basement membrane, the density of which decreased significantly. This decrease in labelling was similar in renal tissues from short- a nd long-term diabetic animals. These results demonstrate that alpha(3) beta(1) present at the podocyte basal plasma membrane facing the glom erular basement membrane, which undergoes important alterations in dia betes, could be involved in the major dysfunctions of the glomerular w all characteristic of diabetic glomerulosclerosis. Since the changes i n integrin were found to occur as early as after 1 month of hyperglyca emia, when morphological alterations of the glomerular basement membra ne are not yet established, we propose that they constitute an early e vent which precedes the onset of diabetic nephropathy.