Low-protein diet attenuates increased gene expression of platelet-derived growth factor and transforming growth factor-beta in experimental glomerular sclerosis.
The present study was designed to assess whether platelet-derived growth factor (PDGF)-A and -B chain and transforming growth factor-beta (TGF-beta) mRNA expression in glomeruli are affected by a low-protein (6%) diet during the course of focal glomerulosclerosis (FGS). Puromycin aminonucleoside (PAN) was injected intraperitoneally in rats, and the right kidney was removed on day 22. The nephrotic rats received successive intraperitoneal injections of PAN on days 27, 34, and 41. Control rats were subjected to a sham operation on day 22. The PAN-injected rats were divided into two groups. Group 1 rats were fed a standard diet containing 22% protein, whereas group 2 rats were fed a low-protein diet containing 6% protein, starting on the same day as the first PAN injection. Rats were killed on days 0, 48, 60, and 80 after the initial PAN injection. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 73% on day 80. The PDGF-A and -B chain and TGF-beta mRNA levels increased significantly as glomerulosclerosis progressed. A positive correlation was noted between the PDGF and TGF-beta mRNA levels and the incidence of glomerular sclerosis. The low-protein diet reduced the prevalence of glomerular sclerosis (10% on day 80) and attenuated the abnormally high expression of PDGF-A and -B chain and TGF-beta genes in FGS glomeruli. These findings suggest that PDGF and TGF contribute to glomerulosclerosis and that a low-protein diet attenuates markedly the increased glomerular expression of the PDGF and TGF-beta genes in glomerular sclerosis.
Fukui
M
M
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Nakamura
T
T
Ebihara
I
I
Nagaoka
I
I
Tomino
Y
Y
Koide
H
H
D000818:Animals; D015870:Gene Expression; D005923:Glomerulosclerosis, Focal Segmental / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D018809:Proliferating Cell Nuclear Antigen; D011488:Protein Deficiency / Q000378:metabolism* / Q000503:physiopathology; D011692:Puromycin Aminonucleoside / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000235:genetics*
D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D011692:Puromycin Aminonucleoside