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 investigated apoptosis, focusing on glomerular endothelial cells during the development of glomerulosclerosis in five-sixths nephrectomized rats for 6 months. Apoptosis was recognized by light and electron microscopy. Biochemical labeling of apoptosis was morphologically confirmed by in situ end labeling of fragmented DNA using terminal deoxynucleotidyltransferase. 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 glomeruli progressed to diffuse sclerosis by months 4–6. During the progression of the disease, the glomerular endothelial cells decreased in number and finally could not be detected in the sclerotic lesion, and apoptotic cells apparently increased in number in the lesion. Significant apoptosis was present from month 3, thereafter it gradually increased to peak by month 6. Double immunostaining for apoptosis and thrombomodulin demonstrated that apoptosis occurred in the glomerular endothelial cells as well as in mesangial cells and infiltrating cells. The number of glomerular endothelial cells with apoptosis increased with the development of glomerulosclerosis, and maximum expression was observed by month 6. We conclude that the depletion of glomerular endothelial cells is associated with apoptosis in the remnant-kidney model, and apoptosis in glomerular endothelial cells may contribute to the development of glomerulosclerosis.