Heparin binding domain of insulin-like growth factor binding protein-5 stimulates mesangial cell migration

The American Journal of Physiology
Christine K AbrassD L Andress

Abstract

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.

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Citations

May 5, 2006·American Journal of Physiology. Cell Physiology·Anne K BerfieldChristine K Abrass
Jan 10, 2009·American Journal of Respiratory Cell and Molecular Biology·Hidekata YasuokaCarol A Feghali-Bostwick
Oct 30, 2009·American Journal of Physiology. Renal Physiology·Valerie SchaefferChristine K Abrass
May 1, 2012·Asian-Australasian Journal of Animal Sciences·X J WangD J Liu

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