ArticleThe Journal of thoracic and cardiovascular surgery2017
Regulation of membrane type-1 matrix metalloproteinase activity and intracellular localization in clinical thoracic aortic aneurysms.
Article in The Journal of thoracic and cardiovascular surgery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Trial
- Thoracic Aortic Aneurysm Development Is Dependent on Membrane Type-1 Matrix Metalloproteinase Activity and Abundance.Biomolecules · 2026Article
- Paradoxical Changes: EMMPRIN Tissue and Plasma Levels in Marfan Syndrome-Related Thoracic Aortic Aneurysms.Journal of clinical medicine · 2024Article
- Tumor-Derived Membrane Vesicles: A Promising Tool for Personalized Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- miR-133a Replacement Attenuates Thoracic Aortic Aneurysm in Mice.Journal of the American Heart Association · 2021Article
- MT1-MMP evaluation in neointimal hyperplasia in the late follow-up after prosthesis implantation.International journal of experimental pathology · 2019Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveMembrane type-1 matrix metalloproteinase (MT1-MMP) is elevated during thoracic aortic aneurysm (TAA) development in mouse models, and plays an important role in the activation of matrix metalloproteinase (MMP)-2 and the release of matrix- bound transforming growth factor-β. In this study, we tested the hypothesis that MT1-MMP is subject to protein kinase C (PKC)-mediated regulation, which alters intracellular trafficking and activity with TAAs.
methodsLevels of MMP-2, native and phosphorylated MT1-MMP, and PKC-δ were measured in aortic tissue from patients with small TAAs (<5 cm; n = 8) and large TAAs (>6.5 cm; n = 8), and compared with values measured in normal controls (n = 8). Cellular localization of green fluorescent protein (GFP)-tagged MT1-MMP was assessed in aortic fibroblasts isolated from control and 4-week TAA mice. The effects of PKC-mediated phosphorylation on MT1-MMP cellular localization and function (active MMP-2 vs phospo-Smad2 abundance) were assessed after treatment with a PKC activator (phorbol-12-myristate-13-acetate [PMA], 100 nM) with and without a PKC-δ-specific inhibitor (röttlerin, 3 μM).
resultsCompared with controls, MT1-MMP abundance was increased in aortas from both TAA groups. Active MMP-2 was increased only in the large TAA group. The abundances of phosphorylated MT1-MMP and activated PKC-δ were enhanced in the small TAA group compared with the large TAA group. MT1-MMP was localized on the plasma membrane in aortic fibroblasts from control mice and in endosomes from TAA mice. Treatment with PMA induced MT1-MMP-GFP internalization, enhanced phospho-Smad2, and reduced MMP-2 activation, whereas röttlerin pretreatment inhibited these effects.
conclusionsPhosphorylation of MT1-MMP mediates its activity through directing cellular localization, shifting its role from MMP-2 activation to intracellular signaling. Thus, targeted inhibition of MT1-MMP may have therapeutic relevance as an approach to attenuating TAA development.
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