Transforming growth factor-beta 1 in hypertensive renal injury in Dahl salt-sensitive rats.
The expression of transforming growth factor-beta 1 (TGF-beta 1) for hypertensive renal injury was investigated in Dahl salt-sensitive (Dahl-S) rats fed a 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-beta biosynthesis by isolated glomeruli, the TGF-beta localization, and the gene expression of TGF-beta 1, latent TGF-beta binding protein (LTBP), and TGF-beta receptors (Types I, II, and III) were compared between the HS rats and LS rats. A TGF-beta bioassay revealed that the isolated glomeruli from the HS rats secreted a larger amount of latent TGF-beta than those from the LS rats. Northern blotting analysis demonstrated that the HS diet led to the increases in cortical gene expression of TGF-beta 1, LTBP, and TGF-beta 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-beta) in the HS rats were elevated, compared with the LS rats. The latent TGF-beta 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-beta 1-positive cells, immunostained by antibody for latency-associated peptide of TGF-beta 1, increased in the glomeruli and vascular walls in the HS rats. These results thus suggested that TGF-beta 1 may be related to hypertensive renal injury in this model.
Tamaki
K
K
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Okuda
S
S
Nakayama
M
M
Yanagida
T
T
Fujishima
M
M
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004039:Diet, Sodium-Restricted; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D006977:Hypertension, Renal / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D007678:Kidney Glomerulus / Q000378:metabolism; D053779:Latent TGF-beta Binding Proteins; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000145:classification / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D005353:Fibronectins; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D017395:Plasminogen Activator Inhibitor 1; D018125:Receptors, Transforming Growth Factor beta; D017673:Sodium Chloride, Dietary; D016212:Transforming Growth Factor beta; D003094:Collagen