Uninephrectomy induces progressive glomerulosclerosis and apoptosis in anti-Thy1 glomerulonephritis.
Administration of the anti-Thy1 antibody in rats induces reversible glomerulonephritis resembling human mesangiolytic and mesangioproliferative diseases. The purpose of the present study was to design a model of irreversible glomerulosclerosis, using the anti-Thy1 antibody injection after uninephrectomy, and examine it, focusing on apoptosis in the process of progressive sclerotic changes. Wistar rats were divided into three groups: one-kidney groups (group I and III) and a two-kidney group (group II). All groups were injected with the anti-Thy1 antibody (OX-7) at day 0, and group I and III were uninephrectomized at day -6. Only group III rats were given a half dose of OX-7 as compared with group I and II. Rats were killed for histological examinations at days 7, 14 and 30. In group I, progressive glomerular lesions, such as glomerular adhesion to Bowman's capsule, crescent formation, and collapse of capillary tufts were observed at days 14 and 30. No significant differences were observed in the pathological findings between group I and III. There was a significantly higher number of glomerular terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells in group I as compared to group II at days 7 and 14. Moreover, the glomerular expression of transforming growth factor-beta, heparan sulfate proteoglycan and chondroitin sulfate proteoglycan significantly increased in group I as compared to group II at days 7 and 14. Progressive glomerulosclerosis can be induced in the rat by a single injection of the anti-Thy1 antibody after unilateral nephrectomy. It is suggested that apoptosis and extracellular matrix accumulation play an important role in the development of glomerulosclerosis.
Sakai
Nobuko
N
Department of Pediatrics, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan. nsatou@fmu.ac.jp
Iseki
Ken
K
Suzuki
Shigeo
S
Mori
Tetsuji
T
Hagino
Seita
S
Zhang
Yuxiang
Y
Yokoya
Sachihiko
S
Kawasaki
Yukihiko
Y
Suzuki
Junzo
J
Isome
Masato
M
Wada
Ikuo
I
Homma
Yoshimi
Y
Suzuki
Hitoshi
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D049109:Cell Proliferation; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology* / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007518:Isoantibodies / Q000009:adverse effects*; D007668:Kidney / Q000473:pathology / Q000601:surgery; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects*; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism
D011508:Chondroitin Sulfate Proteoglycans; D019812:Heparan Sulfate Proteoglycans; D007518:Isoantibodies; D016212:Transforming Growth Factor beta; C035678:anti-Thy antibody