TGF-beta 1 in glomerulosclerosis and interstitial fibrosis of adriamycin nephropathy.

The role of transforming growth factor-beta 1 (TGF-beta 1) for renal injury was investigated in the chronic model of progressive renal disease in rats induced by the injection of adriamycin. The renal cortical tissues were sampled at weeks 4, 8 and 16 for histological examination, either cortical or glomerular cell culture, and RNA extraction. A progressive increase in fibronectin synthesis was found in metabolically labeled cortical or glomerular culture at week 8 or 16, correlating with the degree of glomerulosclerosis and interstitial fibrosis. TGF-beta bioassay (mink lung epithelial cell assay) showed a progressive increase in latent TGF-beta secretion from cortex and glomeruli, while the amount of active TGF-beta was small. The peak of latent TGF-beta levels at week 16 coincided with the intense TGF-beta 1 staining of inflammatory cells dispersed in the interstitium and glomeruli. Northern blotting demonstrated the difference in the mRNA expression patterns of TGF-beta 1 and latent TGF-beta 1 binding protein (LTBP) in the cortex. TGF-beta 1 mRNA was constantly high throughout the experiment, while LTBP mRNA increased progressively and reached a peak at week 16. Furthermore, mRNA levels of fibronectin, procollagen alpha 2(I), and TGF-beta type II and type III receptors increased progressively in a similar pattern to the renal histological changes. These temporal and spacial relationships between the renal histological changes and the increased expression of TGF-beta 1 and TGF-beta receptors may thus suggest that TGF-beta 1 plays an important role in the process of the renal fibrosis and sclerosis.