Transforming growth factor-beta in the development of rat diabetic nephropathy - A 10-month study with insulin-treated rats

We investigated the intrarenal distribution of transforming growth factor-beta(1) (TGF-beta(1)) protein and the TGF-beta(1) mRNA levels in the glomeruli and renal cortex of Wistar rats with streptozotocin-induced diabetes before and after the onset of diabetic nephropathy. Monthly urinary albumin excretion, glomerular filtration rate, glomerular volume, renal histology and immunohistochemical reaction for type-I collagen were also studied. The results showed progressively higher glomerular immunohistochemical TGF-beta(1) staining in rats with a diabetes duration of 24 and 40 weeks which was correlated with albuminuria (r = 0.905, p < 0.01) and was temporally associated with the appearance of glomerular deposition of total and type-I collagen. The glomerular content of TGF-beta(1) mRNA was higher in rats diabetic for 20 weeks while lower cortical RNA-TGF-beta(1) levels were found in rats with a diabetes duration of 1-40 weeks. These data suggest that this polypeptide may be an important mediator of diabetic glomerulosclerosis.