Messenger RNA expression for growth factors in glomeruli from focal glomerular sclerosis.
Focal glomerular sclerosis was induced in rats by chronic injections of puromycin aminonucleoside (PAN) on Days 0, 27, 34, and 41 and by unilateral nephrectomy on Day 22. Rats were sacrificed on Days 0, 8, and 20 (acute phase) and on Days 48, 60, and 80 (sclerotic phase). The percentage of sclerosing glomeruli was 16.6% on Day 48 and increased significantly to 72.8% on Day 80. We examined glomerular mRNA levels for proliferating cell nuclear antigen (PCNA), platelet-derived growth factor (PDGF)-A and B chains, transforming growth factor (TGF)-beta, epidermal growth factor (EGF), insulin-like growth factor (IGF)-I, and basic fibroblast growth factor (bFGF) on Days 0, 8, 20, 48, 60, and 80. Although these growth factor mRNA levels showed little change in glomeruli until Day 20, all growth factor mRNA levels increased in glomeruli during the sclerotic phase of PAN nephrosis as glomerular sclerosis progressed. On Day 80, mRNA levels for PCNA, PDGF-A and B chains, TGF-beta, EGF, IGF-I, and bFGF increased 12-, 10-, 12-, 15-, 2-, 2-, and 8-fold, respectively, in the glomeruli of PAN-treated rats with marked glomerular sclerosis when compared with control rats. Unilateral nephrectomy without PAN administration did not cause glomerular sclerosis up to Day 80 and mRNA levels for PCNA, PDGF-A and -B chains, TGF-beta, EGF, IGF-I, and bFGF in this group were almost the same as those in the normal sham-operated group. These data suggest that changes in growth factor mRNA levels in glomeruli may contribute to the development of PAN-induced glomerular sclerosis.
Nakamura
T
T
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Ebihara
I
I
Fukui
M
M
Osada
S
S
Nagaoka
I
I
Horikoshi
S
S
Tomino
Y
Y
Koide
H
H
D000818:Animals; D015152:Blotting, Northern; D004815:Epidermal Growth Factor / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000473:pathology; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen; D011507:Proteinuria / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000235:genetics
D006133:Growth Substances; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I