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First published online December 17, 2008

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MT1-MMP makes migratory muscle

When blood vessels are injured, vascular smooth muscle cells (VSMCs) contribute to lesion formation by de-differentiating, becoming invasive and migrating into the blood-vessel wall. The matrix metalloproteinase MT1-MMP is known to promote the invasion of VSMCs, and Kaisa Lehti and colleagues (p. 126) now uncover a role for MT1-MMP in the de-differentiation process itself. The authors observe that, in cultured VSMCs, MT1-MMP is dramatically upregulated during de-differentiation (which is measured as the repression of contractile-protein expression). Moreover, de-differentiation is attenuated when MMP inhibitors are present and in MT1-MMP^–/– VSMCs. Growth factors have previously been proposed to promote de-differentiation of VSMCs, and the authors now show that MT1-MMP-dependent de-differentiation requires both PDGF-BB and its receptor, PDGFRβ. In addition, they show that MT1-MMP promotes processing of the receptor LRP1, as well as formation and internalisation of a multiprotein complex containing LRP1, β3 integrin, MT1-MMP and PDGFRβ. Finally, they demonstrate that de-differentiation does not require MT1-MMP when LRP1 is silenced. On the basis of these results, the authors propose a new MT1-MMP-dependent mechanism for VSMC de-differentiation.

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Related articles in JCS:

MT1-MMP promotes vascular smooth muscle dedifferentiation through LRP1 processing

Kaisa Lehti, Nina F. Rose, Sara Valavaara, Stephen J. Weiss, and Jorma Keski-Oja
JCS 2009 122: 126-135. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?