Human glomerular endothelial cells IGFBPs are regulated by IGF-I and TGF-beta1.
The release of insulin-like growth factor binding proteins (IGFBPs) and their regulation in human glomerular endothelial cells (GENC) was characterised. GENC produce IGFBP-4, IGFBP-2 and IGFBP-3 and express mRNA for IGFBP-2 to IGFBP-5. Due to the fact that IGF-I and TGF-beta1 modulate glomerular hypertrophy, their action on IGFBP release and GENC growth was studied. IGF-I increased IGFBP-3, IGFBP-2 and decreased IGFBP-4, while TGF-beta1 decreased IGFBP-3 and apparently increased IGFBP-4. All of the IGFBPs, except the TGF-beta1-regulated IGFBP-4, were modulated at mRNA level. IGF-I stimulated GENC proliferation, while TGF-beta1 inhibited their growth. It was demonstrated that an IGFBP-3 antibody reduced GENC proliferation. However, rhIGFBP-3 alone had no effect on GENC, but after 48 h pre-incubation the IGF-I stimulated GENC growth was increased, suggesting that IGFBP-3 could modulate the IGF-I induced GENC proliferation. It was concluded that the stimulatory IGFBP-3 and the inhibitory IGFBP-4 could regulate GENC growth, although the IGFBP-3 seems to have a predominant effect in this control.
Giannini
S
S
Department of Clinical Pathophysiology, University of Florence, Italy.
Cresci
B
B
Pala
L
L
Ciucci
A
A
Manuelli
C
C
Fujita-Yamaguchi
Y
Y
Cappugi
P
P
Rotella
C M
CM
D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry; D004727:Endothelium / Q000737:chemistry* / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000187:drug effects* / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I