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Study · In vitro (cells) · 2003

2 results

Regulation of vascular smooth muscle cell responses to insulin-like growth factor (IGF)-I by local IGF-binding proteins.

Hsieh T, Gordon RE, Clemmons DR, Busby WH Jr, Duan C

The Journal of biological chemistry12 Aug 2003Cited by 59 (Europe PMC)

PMID12917428 (opens in a new tab)DOI10.1074/jbc.m303835200 (opens in a new tab)PepBankPUB-12917428
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Summary

Insulin-like growth factor (IGF)-I is a pleiotropic hormone that regulates vascular smooth muscle cell (VSMC) migration, proliferation, apoptosis, and differentiation. These actions are mediated by the IGF-I receptor. How activation of the same receptor by the same ligand leads to these diverse cellular responses is not well understood. Here we describe a novel mechanism specifying VSMC responses to IGF-I stimulation, distinctive for the pivotal roles of local IGF-binding proteins (IGFBPs). The role of local IGFBPs was indicated by comparing the activities of IGF-I and des-1-3-IGF-I, an IGF-I analog with reduced binding affinity to IGFBPs. Compared with IGF-I, des-1-3-IGF-I was more potent in stimulating DNA synthesis but much less potent in inducing directed migration of VSMCs. When the effects of individual IGFBPs were tested, IGFBP-2 and IGFBP-4 were found to inhibit IGF-I-stimulated DNA synthesis and migration. IGFBP-5 had an inhibitory effect on IGF-I-stimulated DNA synthesis, but it strongly potentiated IGF-I-induced VSMC migration. By using a non-IGF-binding IGFBP-5 mutant and an IGF-I-neutralizing antibody, it was demonstrated that IGFBP-5 also stimulates VSMC migration in an IGF-independent manner. This effect of IGFBP-5 was inhibited by soluble heparin and by treating cells with heparinase. Mutation of the heparin-binding motif of IGFBP-5 reduced its migration promoting activity. These findings suggest that local IGFBPs are important determinants of cellular responses to IGF-I stimulation, and a key player in this paradigm is IGFBP-5. IGFBP-5 not only modulates IGF-I actions, but it also stimulates cell migration by interacting with cell-surface heparan sulfate proteoglycans.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Activity measurement

    In vascular smooth muscle cells, des-1-3-IGF-I stimulated DNA synthesis more potently than IGF-I.

    In plain wordsIn cells, des-1-3-IGF-I stimulated DNA synthesis more potently than IGF-I.

    Peptide
    IGF-1 DES (des(1-3)IGF-I)
    Outcome
    IncreaseDNA synthesis
    Study

    n: not reported in source

    vascular smooth muscle cells
    Comparator
    IGF-I
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Compared with IGF-I, des-1-3-IGF-I was more potent in stimulating DNA synthesis but much less potent in inducing directed migration of VSMCs.
    1 context sentence
    Summary · context
    The role of local IGFBPs was indicated by comparing the activities of IGF-I and des-1-3-IGF-I, an IGF-I analog with reduced binding affinity to IGFBPs.
  2. 02LabIn vitro (cells)Activity measurement

    In vascular smooth muscle cells, des-1-3-IGF-I induced directed migration less potently than IGF-I.

    In plain wordsIn cells, des-1-3-IGF-I induced directed migration less potently than IGF-I.

    Peptide
    IGF-1 DES (des(1-3)IGF-I)
    Outcome
    DecreaseDirected migration
    Study

    n: not reported in source

    vascular smooth muscle cells
    Comparator
    IGF-I
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Compared with IGF-I, des-1-3-IGF-I was more potent in stimulating DNA synthesis but much less potent in inducing directed migration of VSMCs.
    1 context sentence
    Summary · context
    The role of local IGFBPs was indicated by comparing the activities of IGF-I and des-1-3-IGF-I, an IGF-I analog with reduced binding affinity to IGFBPs.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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