Lumican inhibits angiogenesis by interfering with α2β1 receptor activity and downregulating MMP-14 expression
| Autor: | Mariusz Malinowski, François-Xavier Maquart, Yanusz Wegrowski, Stéphane Brézillon, Magdalena Wiktorska, Radoslaw Bednarek, Jolanta Niewiarowska, Izabela Sacewicz-Hofman, Czeslaw S. Cierniewski |
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| Rok vydání: | 2011 |
| Předmět: |
Lumican
Pathology medicine.medical_specialty Angiogenesis Matrix metalloproteinase inhibitor Down-Regulation Neovascularization Physiologic Matrix Metalloproteinase Inhibitors Matrix metalloproteinase Neovascularization Mice Matrix Metalloproteinase 14 medicine Animals RNA Small Interfering Tube formation Matrigel biology Integrin beta1 Endothelial Cells Hematology Cell biology Chondroitin Sulfate Proteoglycans Proteoglycan Keratan Sulfate biology.protein Integrin alpha2beta1 medicine.symptom |
| Zdroj: | Thrombosis Research. 128:452-457 |
| ISSN: | 0049-3848 |
| DOI: | 10.1016/j.thromres.2011.06.011 |
| Popis: | Article history:Received 1 March 2011Received in revised form 18 May 2011Accepted 13 June 2011Available online 12 July 2011Keywords:LumicanAngiogenesisMetalloproteinasesIntegrinsMetastasis Introduction: Previous studies showed that lumican, a small leucine-rich proteoglycan that binds to α2integrin I domain, is an efficient inhibitor of cell adhesion and migration. In this report, we tested its effect onangiogenesis in vitro and in vivo.Materials and methods: Effect of lumican on angiogenesis was evaluated by in vitro capillary tube formationtest performed between Fibrin II Gels or in Matrigel™ and in vivo by Matrigel ™ plug assay in BALB/c mice.Changes in matrix metalloproteinases expression caused by lumican were analyzed in endothelial cells byreal-time PCR, Western immunoblotting and gelatin zymography.Results: In unchallenged endothelial cells, Matrigel™ induced robust capillary morphogenesis. In contrast,tube formation was dramatically reduced by lumican, and by siRNA to β1 integrin subunit mRNA but not bycontrol siRNA. Similarly, lumican effectively inhibited neovascularization in vivo in assays using Matrigel™plugs formed in BALB/c mice. Interestingly, lumican significantly reduced expression of matrix metallopro-teinases, particularly MMP-14 that is known to activate other MMPs in close vicinity of endothelial cellmembranes.Conclusions: Our results provide strong evidence that lumican affects angiogenesis both by interfering withα2β1 receptor activity and downregulating proteolytic activity associated with surface membranes ofendothelial cells.© 2011 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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