Apoptosis in glomerular sclerosis

Glomerulosclerosis is characterized by progressive extracellular matrix accumulation and glomerular cell loss. The role of glomerular cell apoptosis in glomerulosclerosis was investigated in the rat remnant kidney model and in human glomerular diseases. We identified apoptotic cells in the glomeruli, tubules and interstitium in the remnant kidney by electron microscopy. DNA fragmentation, which is a biochemical characteristic of apoptosis, was detected by in situ nick end-labeling of fragmented DNA with terminal deoxynucleotidyl transferase and biotinylated deoxyuridine triphosphate. Fragmented DNA in the glomeruli and tubules increased with the progression of glomerulosclerosis in the remnant kidney model. This finding was also demonstrated in other glomerular sclerotic lesions such as IgA and lupus nephritis. The number of cells positive for nick end-labeling in the glomerulus significantly correlated with the degree of glomerulosclerosis and the deterioration of renal function. These results indicate that apoptosis is, at least in part, involved in the cell deletion of various glomerular diseases leading to sclerosis.