Heparin binding domain of insulin-like growth factor binding protein-5 stimulates mesangial cell migration.
Insulin-like growth factor I (IGF-I) binding protein-5 (IGFBP-5) is produced by mesangial cells (MCs) and likely functions to modulate glomerular IGF-I activity. Although IGFBP-5 may be inhibitory for IGF-stimulated MC activity, preliminary studies suggested that IGFBP-5 acts directly on MCs. To investigate this further, we evaluated the effects of IGFBP-5 on rat MC migration. We found that the carboxytruncated fragment, IGFBP-5-(1-169), inhibited IGF-I-stimulated migration, but intact IGFBP-5 simulated migration when IGF-I was not present. Demonstration that 125I-labeled IGFBP-5 directly binds to MCs further supports an independent role for IGFBP-5. Because heparin inhibited MC binding of 125I-IGFBP-5, we tested the heparin binding peptide, IGFBP-5-(201-218), for stimulatory activity. IGFBP-5-(201-218) stimulated MC migration, and this effect was inhibited by heparin. Because the disintegrin, kistrin, blocked IGF-I-induced migration but not migration induced by IGFBP-5-(201-218), the migratory induction mechanism for the two peptides is different. These data indicate that separate, specific regions of IGFBP-5 are responsible for interactive effects with IGF-I as well as direct effects on MC activity.
Abrass
C K
CK
Department of Medicine, Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA.
Berfield
A K
AK
Andress
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D018975:Insulin-Like Growth Factor Binding Protein 5; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D006493:Heparin