Recovery of damaged glomerular capillary network with endothelial cell apoptosis in experimental proliferative glomerulonephritis.
Capillary repair can occur in damaged glomeruli in recovery models of glomerulonephritis (GN). In order to clarify whether capillary repair is an essential component in glomerular recovery from GN, we have examined the development of the capillary repair after inflammatory injury in both the repairing glomeruli and the segmental sclerotic scar lesions in Thy-1 GN. Mesangiolytic glomerular damage was induced in rats with anti-Thy-1.1 antibody administration. Diffuse mesangiolysis and segmental microaneurysmal ballooning developed in damaged glomeruli by day 3, with reduction of endothelial cellularity. Thereafter, histological proliferative GN developed between day 5 and week 3. Endothelial cell proliferation began on day 1 and peaked on day 5, and the number of glomerular endothelial cells increased and exceeded the level of control values on day 7. Angiogenic glomerular capillary repair occurred through the process of not only capillary regeneration from remaining endothelial cells in capillary aneurysmal lesions but also new capillary growth derived from the glomerular vascular poles by day 7. The number of glomerular capillary lumina also increased to the level of controls by week 3. Subsequently, mesangial proliferative GN resolved, and most of the glomeruli recovered to their normal structure with the reconstruction of the capillary network by weeks 4-6. In the glomerular capillary repair, significant apoptosis of glomerular endothelial cells was present during the period of mild endothelial cell hypercellularity between day 7 and day 10 (0.06 +/- 0.02 apoptotic endothelial cells/glomerular cross section vs. 0.00 +/- 0.00 in controls, mean +/- SEM; p < 0.05. In Thy-1 GN, most of the damaged glomeruli recovered with angiogenic capillary repair. However, segmental sclerotic scar lesions remained in 10-30% of the glomeruli with an incomplete repair of glomerular capillaries. Therefore, it is concluded that following the destruction of the glomerular capillary network in GN, angiogenic capillary repair plays an essential role in the recovery of damaged glomeruli, and incomplete capillary repair leads to sclerotic scar lesions in damaged glomeruli. Glomerular capillary repair occurs through the process of capillary regeneration from remaining endothelial cells as well as new glomerular capillary growth from the glomerular vascular poles. In glomerular capillary repair, apoptosis is necessary in regulating the number of intrinsic endothelial cells.
Shimizu
A
A
Department of Pathology, Nippon Medical School, Tokyo, Japan.
Masuda
Y
Y
Kitamura
H
H
Ishizaki
M
M
Sugisaki
Y
Y
Yamanaka
N
N
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001710:Biotin; D002196:Capillaries / Q000166:cytology; D053938:DNA Fragmentation; D003856:Deoxyuracil Nucleotides; D004730:Endothelium, Vascular / Q000166:cytology* / Q000648:ultrastructure; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009393:Nephritis / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling
D003856:Deoxyuracil Nucleotides; D001710:Biotin