Human glomerular endothelial cells IGFBPs are regulated by IGF-I and TGF-beta(1)

The release of insulin-like growth factor binding proteins (IGFBPs) and the ir regulation in human glomerular endothelial cells (GENC) was characterise d. GENC produce IGFBP-4, IGFBP-2 and IGFBP-3 and express mRNA for IGFBP-2 t o IGFBP-5. Due to the fact that IGF-I and TGF-beta(1) modulate glomerular h ypertrophy, their action on IGFBP release and GENC growth was studied. IGF- I increased IGFBP-3, IGFBP-2 and decreased IGFBP-4, while TGF-beta(1) decre ased IGFBP-3 and apparently increased IGFBP4. All of the IGFBPs, except the TGF-beta(1)-regulated IGFBP-4, were modulated at mRNA level. IGF-I stimula ted GENC proliferation, while TGF-beta(2) inhibited their growth. It was de monstrated that an IGFBP-3 antibody reduced GENC proliferation. However, rh IGFBP-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 modul ate the IGF-I induced GENC proliferation. It was concluded that the stimula tory IGFBP-3 and the inhibitory IGFBP-4 could regulate GENC growth, althoug h the IGFBP-3 seems to have a predominant effect in this control. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.