| MMP-9 controls Schwann cell proliferation and phenotypic remodeling via IGF-1 and ErbB receptor-mediated activation of MEK/ERK pathway. | |
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MedLine Citation:
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PMID: 19229995 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Phenotypic remodeling of Schwann cells is required to ensure successful regeneration of damaged peripheral axons. After nerve damage, Schwann cells produce an over 100-fold increase in metalloproteinase-9 (MMP-9), and therapy with an MMP inhibitor increases the number of resident (but not infiltrating) cells in injured nerve. Here, we demonstrate that MMP-9 regulates proliferation and trophic signaling of Schwann cells. Using in vivo BrdU incorporation studies of axotomized sciatic nerves of MMP-9-/- mice, we found increased Schwann cell mitosis in regenerating (proximal) stump relative to wild-type mice. Treatment of cultured primary Schwann cells with recombinant MMP-9 suppressed their growth, mitogenic activity, and produced a dose-dependent, biphasic, and selective activation of ERK1/2, but not JNK and p38 MAPK. MMP-9 induced ERK1/2 signaling in both undifferentiated and differentiated (using dbcAMP) Schwann cells. Using inhibitors to MEK and trophic tyrosine kinase receptors, we established that MMP-9 regulates Ras/Raf/MEK-ERK pathways through IGF-1, ErbB, and PDGF receptors. We also report on the early changes of MMP-9 mRNA expression (within 24 h) after axotomy. These studies establish that MMP-9 controls critical trophic signal transduction pathways and phenotypic remodeling of Schwann cells. |
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Authors:
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Sharmila Chattopadhyay; Veronica I Shubayev |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Glia Volume: 57 ISSN: 1098-1136 ISO Abbreviation: Glia Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-07-20 Completed Date: 2009-11-02 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8806785 Medline TA: Glia Country: United States |
Other Details:
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Languages: eng Pagination: 1316-25 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, University of California, San Diego, California 92093-0629, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation* Cells, Cultured Extracellular Signal-Regulated MAP Kinases / metabolism Female Insulin-Like Growth Factor I / metabolism MAP Kinase Kinase Kinases / metabolism MAP Kinase Signaling System Matrix Metalloproteinase 9 / genetics, metabolism* Mice Mice, Knockout Phenotype RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Receptor Protein-Tyrosine Kinases / metabolism Receptors, Platelet-Derived Growth Factor / metabolism Schwann Cells / cytology*, physiology* Sciatic Nerve / injuries, physiology |
| Grant Support | |
ID/Acronym/Agency:
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R21 NS060307-01/NS/NINDS NIH HHS; R21 NS060307-01/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/Receptors, Platelet-Derived Growth Factor; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.25/MAP Kinase Kinase Kinases; EC 3.4.24.-/Mmp9 protein, mouse; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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