APOPTOSIS IN GLOMERULAR SCLEROSIS

Glomerulosclerosis is characterized by progressive extracellular matri x accumulation and glomerular cell loss. The role of glomerular cell a poptosis in glomerulosclerosis was investigated in the rat remnant kid ney model and in human glomerular diseases. We identified apoptotic ce lls in the glomeruli, tubules and interstitium in the remnant kidney b y electron microscopy. DNA fragmentation, which is a biochemical chara cteristic of apoptosis, was detected by in situ nick end-labeling of f ragmented DNA with terminal deoxynucleotidyl transferase and biotinyla ted deoxyuridine triphosphate. Fragmented DNA in the glomeruli and tub ules increased with the progression of glomerulosclerosis in the remna nt kidney model. This finding was also demonstrated in other glomerula r sclerotic lesions such as IgA and lupus nephritis. The number of cel ls positive for nick end-labeling in the glomerulus significantly corr elated 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 lea ding to sclerosis.