title: Inhibition of capillary repair in proliferative glomerulonephritis results in persistent glomerular inflammation with glomerular sclerosis.
abstract: The pathological process of glomerulonephritis (GN) includes glomerular capillary damage, and vascular endothelial growth factor (VEGF) has an important role in glomerular capillary repair in GN. We examined the effect of inhibition of glomerular capillary repair after capillary injury in GN. Experimental Thy-1 GN was induced in rats that were divided into two groups: rats that received anti-VEGF neutralizing antibody (50 μg per 100 g body weight per day) and those treated with the vehicle from day 2 to day 9. We assessed the renal function and histopathology serially until week 6. Rats of the Thy-1 GN group showed diffuse glomerular mesangiolysis with ballooning destruction of the capillary network by day 3. VEGF(164) protein levels increased in the damaged glomeruli during days 5 to 10, and endothelial-cell proliferation increased with capillary repair in the vehicle-injected group. Proliferative GN resolved subsequently with decreased mesangial hypercellularity, and recovery of most of the glomeruli to the normal structure was evident by week 6. In contrast, administration of anti-VEGF antibody significantly decreased endothelial-cell proliferation and capillary repair in glomeruli by week 2. Thereafter, glomerular mesangial-cell proliferation and activation continued with persistent infiltration of macrophages. At week 6, segmental glomerular sclerosis developed with mesangial matrix accumulation and proteinuria. Deposition of type I collagen was also noted in sclerotic lesions. We conclude that impaired capillary repair was the underlying mechanism in the prolongation of glomerular inflammation in proliferative GN and in the development of glomerular sclerosis. Capillary repair has an important role in the recovery of glomerular damage and in the resolution of proliferative GN.
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Masuda
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Mitue
authors.initials: M
authors.lastname: Kataoka
authors.forename: Takashi
authors.initials: T
authors.lastname: Arai
authors.forename: Arimi
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Xuanyi
authors.initials: X
authors.lastname: Du
authors.forename: Sabine Kyoko
authors.initials: SK
authors.lastname: Saito
authors.forename: Kaoru
authors.initials: K
authors.lastname: Aki
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagasaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Mii
authors.forename: Emiko
authors.initials: E
authors.lastname: Fujita
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007249:Inflammation; D007518:Isoantibodies / Q000276:immunology; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D007518:Isoantibodies; D042461:Vascular Endothelial Growth Factor A; C035678:anti-Thy antibody; C467498:vascular endothelial growth factor A, rat