Uninephrectomy induces progressive glomerulosclerosis and apoptosis in anti‐Thy1 glomerulonephritis

Abstract

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.

Gene expression profile and overexpression of apoptosis-related genes (NGFI-B and Gadd 45 γ) in early phase of Thy-1 nephritis model

“…GMC apoptosis can contribute to the initiation and development of Thy-1 N, although the exact pathogenesis has not been clarified until now. However, for the treatment of progressive Thy-1 N, the blockage of cell apoptosis by the inhibition of the early apoptotic process, such as knocking out or down some apoptosis-related genes or cutting signals of cell apoptosis before the appearance of DNA fragmentation (Sakai et al 2005), would be useful.…”

Glomerular Expression of Hydrogen Peroxide-Inducible Clone-5 in Human and Rat Progressive Mesangial Proliferative Glomerulonephritis

“…Although we did not examine the association between MC Hic-5 expression and MC apoptosis in this study, a previous study showed that a significant MC apoptosis occurred in the relatively early phase (days 7 and 14) in the same GN model [29]. Therefore, we speculated that the MC phenotype, which co-expressed Hic-5 and α-SMA in the advanced stage in this GN model, was not actively associated with MC apoptosis.…”

Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats

“…These results comes in agreement with many investigators who indicated that anti-Thy1 induced apoptosis in different animals. Sakai et al reported that anti-Thy1 induced necrosis and DNA fragmentation in Wistar rats [27] . Moreover, the glomerular expression of TGF-β, heparan sulfate proteoglycan and chondroitin sulfate proteoglycan were significantly increased.…”