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 pr ogressive mesangial expansion with collapse of capillary lumina, inter stitial fibrosis and mononuclear cellular infiltration. Transforming g rowth factor-beta (TGF-beta(1)) is an important regulator of extracell ular matrix formation. The purpose of this study was to investigate th e production and distribution of TGF-beta(1) in the kidney during the development of glomerulosclerosis and renal fibrosis in rats with subt otal renal ablation. Eighty-two female Wistar rats weighing 180-220 g were divided into two groups: 49 rats were subjected to 5/6 renal abla tion and 33 to sham operation. Urinary albumin excretion, blood pressu re and glomerular filtration rate (GFR) were evaluated after the surgi cal procedure. We also performed histology and immunohistochemistry an d determined mRNA for TGF-beta(1) in the kidneys of these rats 8, 15, 30 and 90 days after operation. The results showed progressively highe r 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 ass ociation between glomerulosclerosis, interstitial fibrosis and intense mononuclear cellular infiltration on the one hand and higher immunohi stochemical TGF-beta(1) staining in the renal cortex on the other show that this polypeptide may contribute to the development of renal fibr osis in this model.