Transforming growth factor-β1 in hypertensive renal injury in Dahl salt-sensitive rats

Abstract

The expression of transforming growth factor-β1 (TGFβ1) for hypertensive renal injury was investigated in Dahl salt-sensitive (Dahl-S) rats fed NaCl high-salt (HS; 8% NaCl) diet or a low-salt (LS; 0.3% NaCl) diet for 4 wk. The HS rats developed severe hypertension and renal damage, including glomerulosclerosis and arteriosclerosis. TGF-β biosynthesis by isolated glomeruli, the TGF-β localization, and the gene expression of TGF- β, latent TGF-β binding protein (LTBP), and TGF-β receptors (Types I, II, and III) were bioassays between the HS rats and LS rats. A TGF-α bioassay revealed that the isolated glomeruli from the HS rats secreted a larger amount of latent TGF-β than those from the LS rats. Northern blotting analysis demonstrated that the HS diet led to the increases in cortical gene expression of TGF-β1, LTBP, and TGF-β receptors), compared with the LS diet. The glomerular biosynthesis of fibronectin and plasminogen activator inhibitor-1 (PAI-1), and cortical mRNA expression for fibronectin, collagen I, and PAI-1 (which may be affected by TGF-β) in the HS rats were elevated, compared with the LS rats. The latent TGF-β immunostained by anti-LTBP antibody was localized on the sclerosing glomeruli and vascular walls. Furthermore, fibronectin, collagen I, and PAI-1 were also localized in the sclerotic area. The TGF-β1-positive cells, immunostained by antibody for latency-associated peptide of TGF-β1, increased in the glomeruli and vascular walls in the HS rats. These results thus suggested that TGF-β1 may be related to hypertensive renal injury in this model.