| Glucose regulation of thrombospondin and its role in the modulation of smooth muscle cell proliferation. | |
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MedLine Citation:
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PMID: 20689700 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Smooth muscle cells (SMC) maintained in high glucose are more responsive to IGF-I than those in normal glucose. There is significantly more thrombospondin-1 (TSP-1) in extracellular matrix surrounding SMC grown in 25 mM glucose. In this study we investigated 1) the mechanism by which glucose regulates TSP-1 levels and 2) the mechanism by which TS-1 enhances IGF-I signaling. The addition of TSP-1 to primary SMC was sufficient to enhance IGF-I responsiveness in normal glucose. Reducing TSP-1 protein levels inhibited IGF-I signaling in SMC maintained in high glucose. We determined that TSP-1 protected IAP/CD47 from cleavage and thereby facilitated its association with SHP substrate-1 (SHPS-1). We have shown previously that the hyperglycemia induced protection of IAP from cleavage is an important component of the ability of hyperglycemia to enhance IGF-I signaling. Furthermore we determined that TSP-1 also enhanced phosphorylation of the beta3 subunit of the alphaVbeta3 integrin, another molecular event that we have shown are critical for SMC response to IGF-I in high glucose. Our studies also revealed that the difference in the amount of TSP-1 in the two different glucose conditions was due, at least in part, to a difference in the cellular uptake and degradation of TSP-1. |
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Authors:
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Laura A Maile; Lee B Allen; Christopher F Hanzaker; Katherine A Gollahon; Paul Dunbar; David R Clemmons |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-20 |
Journal Detail:
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Title: Experimental diabetes research Volume: 2010 ISSN: 1687-5303 ISO Abbreviation: Exp Diabetes Res Publication Date: 2010 |
Date Detail:
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Created Date: 2010-08-06 Completed Date: 2010-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101274844 Medline TA: Exp Diabetes Res Country: United States |
Other Details:
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Languages: eng Pagination: - Citation Subset: IM |
Affiliation:
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Division of Endocrinology, University of North Carolina, CB# 7170, 5030 Burnett Womack, Chapel Hill, NC 27599-7170, USA. laura_maile@med.unc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD47 / metabolism Cell Proliferation* Glucose / metabolism*, pharmacology Hyperglycemia / metabolism* Insulin-Like Growth Factor I / metabolism* Integrin alphaVbeta3 / metabolism Male Myocytes, Smooth Muscle / drug effects, metabolism, physiology* Phosphorylation Swine Thrombospondin 1 / metabolism*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD47; 0/Integrin alphaVbeta3; 0/Thrombospondin 1; 50-99-7/Glucose; 67763-96-6/Insulin-Like Growth Factor I |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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