APOPTOSIS IN GLOMERULAR ENDOTHELIAL-CELLS DURING THE DEVELOPMENT OF GLOMERULOSCLEROSIS IN THE REMNANT-KIDNEY MODEL

Capillary obsolescence with subsequent glomerulosclerosis is a common finding in most progressive glomerular diseases. In this study we inve stigated apoptosis, focusing on glomerular endothelial cells during th e development of glomerulosclerosis in five-sixths nephrectomized rats for 6 months. Apoptosis was recognized by light and electron microsco py. Biochemical labeling of apoptosis was morphologically confirmed by in situ end labeling of fragmented DNA using terminal deoxynucleotidy ltransferase. Glomerular endothelial cells were identified by electron microscope and immunostaining for thrombomodulin which is known to be an endothelial cell surface glycoprotein. Glomerular hypercellularity occurred by month 2, peaking by month 3, and an extracellular matrix accumulation was evident by month 3. Subsequently, most of the glomeru li progressed to diffuse sclerosis by months 4-6. During the progressi on of the disease, the glomerular endothelial cells decreased in numbe r and finally could not be detected in the sclerotic lesion, and apopt otic cells apparently increased in number in the lesion. Significant a poptosis was present from month 3, thereafter it gradually increased t o peak by month 6. Double immunostaining for apoptosis and thrombomodu lin demonstrated that apoptosis occurred in the glomerular endothelial cells as well as in mesangial cells and infiltrating cells. The numbe r of glomerular endothelial cells with apoptosis increased with the de velopment of glomerulosclerosis, and maximum expression was observed b y month 6. We conclude that the depletion of glomerular endothelial ce lls is associated with apoptosis in the remnant-kidney model, and apop tosis in glomerular endothelial cells may contribute to the developmen t of glomerulosclerosis.