Document Detail

MMP-9 controls Schwann cell proliferation and phenotypic remodeling via IGF-1 and ErbB receptor-mediated activation of MEK/ERK pathway.
MedLine Citation:
PMID:  19229995     Owner:  NLM     Status:  MEDLINE    
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.
Sharmila Chattopadhyay; Veronica I Shubayev
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Glia     Volume:  57     ISSN:  1098-1136     ISO Abbreviation:  Glia     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-07-20     Completed Date:  2009-11-02     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8806785     Medline TA:  Glia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1316-25     Citation Subset:  IM    
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MeSH Terms
Cell Proliferation*
Cells, Cultured
Extracellular Signal-Regulated MAP Kinases / metabolism
Insulin-Like Growth Factor I / metabolism
MAP Kinase Kinase Kinases / metabolism
MAP Kinase Signaling System
Matrix Metalloproteinase 9 / genetics,  metabolism*
Mice, Knockout
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Receptor Protein-Tyrosine Kinases / metabolism
Receptors, Platelet-Derived Growth Factor / metabolism
Schwann Cells / cytology*,  physiology*
Sciatic Nerve / injuries,  physiology
Grant Support
R21 NS060307/NS/NINDS NIH HHS; R21 NS060307-01/NS/NINDS NIH HHS; R21 NS060307-01/NS/NINDS NIH HHS
Reg. No./Substance:
0/RNA, Messenger; 67763-96-6/Insulin-Like Growth Factor I; EC Protein-Tyrosine Kinases; EC, Platelet-Derived Growth Factor; EC Signal-Regulated MAP Kinases; EC Kinase Kinase Kinases; EC 3.4.24.-/Mmp9 protein, mouse; EC Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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