Transforming growth factor-beta production during the development of renal fibrosis in rats with subtotal renal ablation

The histologic changes observed in the remnant kidney model include progressive mesangial expansion with collapse of capillary lumina, interstitial fibrosis and mononuclear cellular infiltration. Transforming growth factor-beta (TGF-beta(1)) is an important regulator of extracellular matrix formation. The purpose of this study was to investigate the production and distribution of TGF-beta(1) in the kidney during the development of glomerulosclerosis and renal fibrosis in rats with subtotal renal ablation. Eighty-two female Wistar rats weighing 180-220 g were divided into two groups: 49 rats were subjected to 5/6 renal ablation and 33 to sham operation. Urinary albumin excretion, blood pressure and glomerular filtration rate (GFR) were evaluated after the surgical procedure. We also performed histology and immunohistochemistry and determined mRNA for TGF-beta(1) in the kidneys of these rats 8, 15, 30 and 90 days after operation. The results showed progressively higher immunohistochemical TGF-beta(1) staining in rats with subtotal renal ablation. Cortical renal content of TGF-beta(1) mRNA was also higher in these animals and peaked at day 15. The existence of a temporal association between glomerulosclerosis, interstitial fibrosis and intense mononuclear cellular infiltration on the one hand and higher immunohistochemical TGF-beta(1) staining in the renal cortex on the other show that this polypeptide may contribute to the development of renal fibrosis in this model.