Vulnerability of progeroid smooth muscle cells to biomechanical forces is mediated by MMP13
| Autor: | Guillem Colell, Rodrigo L. dos Santos, Luís Miguel Monteiro, Andreia Bernardo, Claire Navarro, Nicolas Lévy, Lino Ferreira, Anna Rosell, Anne-Laure Egesipe, Daniel Thornton, Xavier Nissan, João Pedro de Magalhães, James C. Smith, Alessandro Ori, Karim Harhouri, Luís M.B.B. Estronca, Deolinda Santinha, Helena Vazão, Tania Rafaela Vale Carvalho, Annachiara De Sandre-Giovannoli, Patrícia R. Pitrez |
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| Přispěvatelé: | University of Coimbra [Portugal] (UC), Universitat Autònoma de Barcelona (UAB), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Liverpool, ProGeLife [Marseille], Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Universidade de Lisboa = University of Lisbon (ULISBOA), Mogrify Ltd [Cambridge, Royaume-Uni], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Francis Crick Institute [London], Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Leibniz Association, Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was funded by FEDER through the Program COMPETE and by Portuguese fund through FCT in context of the projects EXPL/BIM-MED/2267/2013 and POCI-01-0145-FEDER-029229, as well as the European project ERAatUC (ref. 669088). PRP wishes to thank FCT for a BD fellowship (SFRH/BD/71042/2010). AR is supported by the Miguel Servet research contract CPII15/00003 from Instituto de Salud Carlos III, Spain. The FLI is a member of the Leibniz Association and is financially supported by the Federal Government of Germany and the State of Thuringia. The authors gratefully acknowledge support from the FLI proteomics core facility., Repositório da Universidade de Lisboa, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases [Corbeil-Essonnes] (I-Stem), Universidade de Lisboa (ULISBOA), Molecular Genetics Laboratory [Marseille], Department of Medical Genetics [Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital de la Timone [CHU - APHM] (TIMONE), Bodescot, Myriam |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Proteomics health care facilities manpower and services General Physics and Astronomy 02 engineering and technology Matrix metalloproteinase Stem-cell biotechnology Mice Progeria Smooth muscle Heart Rate Induced pluripotent stem cell lcsh:Science health care economics and organizations Metalloproteinase Multidisciplinary integumentary system 021001 nanoscience & nanotechnology Lamin Type A 3. Good health Cell biology Cardiovascular diseases Cardiovascular Diseases cardiovascular system Female 0210 nano-technology Biotechnology Premature aging congenital hereditary and neonatal diseases and abnormalities Science education Induced Pluripotent Stem Cells Myocytes Smooth Muscle [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Matrix Metalloproteinase Inhibitors General Biochemistry Genetics and Molecular Biology Article Glycocalyx 03 medical and health sciences Downregulation and upregulation Matrix Metalloproteinase 13 medicine Animals [SDV.BC] Life Sciences [q-bio]/Cellular Biology nutritional and metabolic diseases General Chemistry medicine.disease Mice Mutant Strains 030104 developmental biology lcsh:Q |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Nature Communications Nature Communications, 2020, 11 (1), pp.4110. ⟨10.1038/s41467-020-17901-2⟩ Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.4110. ⟨10.1038/s41467-020-17901-2⟩ Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| ISSN: | 2041-1723 |
| Popis: | © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detach from the chip after a few days of culture; this process is mediated by the upregulation of metalloprotease 13 (MMP13). Importantly, double-mutant LmnaG609G/G609GMmp13-/- mice or LmnaG609G/G609GMmp13+/+ mice treated with a MMP inhibitor show lower SMC loss in the aortic arch than controls. MMP13 upregulation appears to be mediated, at least in part, by the upregulation of glycocalyx. Our HGPS-SMCs chip represents a platform for developing treatments for HGPS individuals that may complement previous pre-clinical and clinical treatments. This work was funded by FEDER through the Program COMPETE and by Portuguese fund through FCT in context of the projects EXPL/BIM-MED/2267/2013 and POCI-01-0145-FEDER-029229, as well as the European project ERAatUC (ref. 669088).PRP wishes to thank FCT for a BD fellowship (SFRH/BD/71042/2010). AR is supported by the Miguel Servet research contract CPII15/00003 from Instituto de Salud Carlos III, Spain. The FLI is a member of the Leibniz Association and is financiallysupported by the Federal Government of Germany and the State of Thuringia. The authors gratefully acknowledge support from the FLI proteomics core facility. |
| Databáze: | OpenAIRE |
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