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Here, we demonstrate that MMP\u20109 regulates proliferation and trophic signaling of Schwann cells. Using <jats:italic>in vivo<\/jats:italic> BrdU incorporation studies of axotomized sciatic nerves of MMP\u20109\u2212\/\u2212 mice, we found increased Schwann cell mitosis in regenerating (proximal) stump relative to wild\u2010type mice. Treatment of cultured primary Schwann cells with recombinant MMP\u20109 suppressed their growth, mitogenic activity, and produced a dose\u2010dependent, biphasic, and selective activation of ERK1\/2, but not JNK and p38 MAPK. MMP\u20109 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\u20109 regulates Ras\/Raf\/MEK\u2014ERK pathways through IGF\u20101, ErbB, and PDGF receptors. We also report on the early changes of MMP\u20109 mRNA expression (within 24 h) after axotomy. These studies establish that MMP\u20109 controls critical trophic signal transduction pathways and phenotypic remodeling of Schwann cells. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20851","type":"journal-article","created":{"date-parts":[[2009,2,19]],"date-time":"2009-02-19T19:15:44Z","timestamp":1235070944000},"page":"1316-1325","source":"Crossref","is-referenced-by-count":93,"title":["MMP\u20109 controls Schwann cell proliferation and phenotypic remodeling via IGF\u20101 and ErbB receptor\u2010mediated activation of MEK\/ERK pathway"],"prefix":"10.1002","volume":"57","author":[{"given":"Sharmila","family":"Chattopadhyay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica 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