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dc.contributor.authorToriseva, Mervi
dc.contributor.authorLaato, Matti
dc.contributor.authorCarpén, Olli
dc.contributor.authorRuohonen, Suvi T.
dc.contributor.authorSavontaus, Eriika
dc.contributor.authorInada, Masaki
dc.contributor.authorKrane, Stephen Martin
dc.contributor.authorKähäri, Veli-Matti
dc.date.accessioned2013-03-26T20:49:10Z
dc.date.issued2012
dc.identifier.citationToriseva, Mervi, Matti Laato, Olli Carpén, Suvi T. Ruohonen, Eriika Savontaus, Masaki Inada, Stephen M. Krane, and Veli-Matti Kähäri. 2012. MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability. PLoS ONE 7(8): e42596.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10467407
dc.description.abstractProteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13) in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13−/−) and wild type (WT) mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42%) at day 21 in Mmp13−/− mice. Granulation tissue in Mmp13−/− mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13−/− mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13−/− mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13−/− granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13−/− mice compared to WT mice. Mmp13−/− mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0042596en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413640/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectSkinen_US
dc.subjectSkin Physiologyen_US
dc.subjectBiochemistryen_US
dc.subjectEnzymesen_US
dc.subjectEnzyme Classesen_US
dc.subjectCollagenaseen_US
dc.subjectProteinsen_US
dc.subjectExtracellular Matrix Proteinsen_US
dc.subjectGeneticsen_US
dc.subjectMolecular Geneticsen_US
dc.subjectGene Regulationen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectGene Expressionen_US
dc.titleMMP-13 Regulates Growth of Wound Granulation Tissue and Modulates Gene Expression Signatures Involved in Inflammation, Proteolysis, and Cell Viabilityen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorKrane, Stephen Martin
dc.date.available2013-03-26T20:49:10Z
dc.identifier.doi10.1371/journal.pone.0042596*
dash.contributor.affiliatedKrane, Stephen Martin


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