Characterization of insulin-like growth factor binding proteins and regulation of IGFBP3 in human mesangial cells

Pascale Grellier, Michael Sabbah, Bruno Fouqueray, Kathleen Woodruff, Douglas Yee, Hanna E. Abboud, Sherry L. Abboud

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

IGF-I regulates renal growth and development. Insulin-like growth factor binding proteins (IGFBPs) are synthesized by the kidney and may modulate the local autocrine and/or paracrine actions of IGF-I. We have previously demonstrated that mesangial cells (MC) release IGF-I and IGF-binding activity; however, the specific IGFBPs produced by these cells and the factors involved in their regulation are unknown. We examined MC for expression of IGFBP-1 to -6 mRNAs and proteins. RNase protection assays using total RNA demonstrated that MC express all of the IGFBPs. [125I]IGF-I Western ligand blot of conditioned medium demonstrated that MC release IGFBPs of 24, 29, 32 kDa, and a doublet at 46 kDa, consistent with IGFBP-4, -5, -2 and -3, respectively. IGFBP species of 28 and 34 kDa were also detected. Since IGF-I and TGF-β are implicated in glomerular hypertrophy and matrix expansion, we tested their effect on IGFBPs released by MC. IGF-I (100 ng/ml), TGF-β (2 ng/ml) and forskolin (10-5 M) differentially regulated the abundance of IGFBPs released in the conditioned medium in a time-dependent manner. IGF-I and TGF-beta were potent inducers of the release of IGFBP3 protein; however, TGF-β, but not IGF-I, increased IGFBP3 mRNA levels. Recombinant IGFBP3 was tested for its effect on IGF-I-induced mitogenesis. IGFBP3 inhibited IGF-I-stimulated DNA synthesis in a dose-dependent manner with a peak effect observed at 50 nM IGFBP3. Although TGF-β is a potent inhibitor of IGF-I-stimulated DNA synthesis, this effect is not mediated via IGFBPs. Expression of IGFBP-1 to -6 by MC suggests that these proteins may modulate IGF-I bioavailability in the glomerulus. IGF-I itself, TGF-β and cAMP agonists may indirectly modulate the effects of IGF-I via the release of IGFBPs by MC.

Original languageEnglish (US)
Pages (from-to)1071-1078
Number of pages8
JournalKidney International
Volume49
Issue number4
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Characterization of insulin-like growth factor binding proteins and regulation of IGFBP3 in human mesangial cells'. Together they form a unique fingerprint.

  • Cite this