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.