Apoptosis in the repair process of experimental proliferative glomerulonephritis.

The recovery from the proliferative glomerulonephritis (GN) with reduction of hypercellularity is known in various experimental and human GN. To elucidate the participation of apoptosis in GN, we studied the experimental Thy-1.1 GN for six weeks. Apoptosis was recognized by both light and electron microscopy, and the biochemical expression of apoptosis was morphologically confirmed by in situ end-labeling method of fragmented DNA, using terminal deoxy-transferase. Mesangioproliferative GN was induced by a single administration of anti-Thy-1.1 monoclonal antibody in a rat. Mesangial cell proliferation started early in the process and the number of glomerular cells peaked from day 7 to day 10. Subsequently, the degree of proliferative lesion diminished with obvious reconstruction of the capillary structure, as well as decrease in the number of glomerular cells. During this period, proliferated mesangial cells returned to their original level of cellularity and apoptosis apparently increased in number among the glomeruli. Apoptosis was significantly noted from day 7 to week 4 and was in its maximum at day 10 to week 2. Following this period, by week 6 most of the glomeruli reverted to their original structure. The number of infiltrated neutrophils and macrophages in the glomeruli slowly decreased during the course of the disease, and a few apoptosis were also observed. It is concluded that proliferated glomerular cells regress by apoptosis in the repairing process of GN. Apoptosis plays an essential role in the recovery to the original glomerular structure in GN.