The FibromiR miR-214-3p Is Upregulated in Duchenne Muscular Dystrophy and Promotes Differentiation of Human Fibro-Adipogenic Muscle Progenitors
| العنوان: | The FibromiR miR-214-3p Is Upregulated in Duchenne Muscular Dystrophy and Promotes Differentiation of Human Fibro-Adipogenic Muscle Progenitors |
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| المؤلفون: | Claude J. Dechesne, Georges Vassaux, Julien Fassy, Virginie Magnone, Claudine Moratal, Nicolas Nottet, Noémie Clément, Nicolas Pottier, Pascal Peraldi, Nicole Arrighi, Romain Larrue, Kevin Lebrigand, Sandy Fellah, Bernard Mari, Christian Dani, Nicolas Pons, Grégoire Savary |
| المساهمون: | Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), This work was supported by funds from Institut National de la Santé et de la Recherche Médicale (Inserm), Centre National de la Recherche Scientifique (CNRS), the « Association Française contre les Myopathies, AFM (through grant HuMusmiR #17708 and a PhD fellowship for CM), the French Government (Agence Nationale de Recherche, ANR) ANR-PRCI FIBROMIR, the Investments for the Future LABEX SIGNALIFE (ANR-11-LABX-0028- 551 01), the Netherland Duchenne Parent Project and ITMO Cancer Aviesan (Alliance Nationale pour les Sciences de la Vie et de la Santé, National Alliance for Life Science and Health) within the framework of the Cancer Plan (Plan Cancer 2018 ARN non-codants en cancérologie: du fondamental au translationnel n° 18CN045)., ANR-18-CE92-0009,FIBROMIR,MicroARN et Interactions Epithélio-Mesenchymateuses dans les Pathologies Pulmonaires(2018), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), RUIZ, Caroline, APPEL À PROJETS GÉNÉRIQUE 2018 - MicroARN et Interactions Epithélio-Mesenchymateuses dans les Pathologies Pulmonaires - - FIBROMIR2018 - ANR-18-CE92-0009 - AAPG2018 - VALID, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID |
| المصدر: | Cells, Vol 10, Iss 1832, p 1832 (2021) Cells Cells, MDPI, 2021, 10 (7), pp.1832. ⟨10.3390/cells10071832⟩ Cells, 2021, 10 (7), pp.1832. ⟨10.3390/cells10071832⟩ Volume 10 Issue 7 |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Duchenne muscular dystrophy, Muscle Development, microRNA (miRNA), 0302 clinical medicine, Fibrosis, Adipocytes, Medicine, Biology (General), Child, Myofibroblasts, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adipogenesis, Stem Cells, Cell Differentiation, General Medicine, Middle Aged, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], transforming growth factor beta (TGFβ), Female, Fibroblast Growth Factor 2, Myofibroblast, Signal Transduction, Adult, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, QH301-705.5, Population, Article, Transforming Growth Factor beta1, 03 medical and health sciences, Downregulation and upregulation, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Humans, Receptor, Fibroblast Growth Factor, Type 1, Progenitor cell, education, Muscle, Skeletal, Base Sequence, business.industry, Gene Expression Profiling, fibrosis, Skeletal muscle, medicine.disease, fibro-adipogenic progenitor (FAP), Muscular Dystrophy, Duchenne, MicroRNAs, 030104 developmental biology, FGFR1, Gene Expression Regulation, Duchenne muscular dystrophy (DMD), Cancer research, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | International audience; Fibrosis is a deleterious invasion of tissues associated with many pathological conditions, such as Duchenne muscular dystrophy (DMD) for which no cure is at present available for its prevention or its treatment. Fibro-adipogenic progenitors (FAPs) are resident cells in the human skeletal muscle and can differentiate into myofibroblasts, which represent the key cell population responsible for fibrosis. In this study, we delineated the pool of microRNAs (miRNAs) that are specifically modulated by TGFβ1 in FAPs versus myogenic progenitors (MPs) by a global miRNome analysis. A subset of candidates, including several “FibromiRs”, was found differentially expressed between FAPs and MPs and was also deregulated in DMD versus healthy biopsies. Among them, the expression of the TGFβ1-induced miR-199a~214 cluster was strongly correlated with the fibrotic score in DMD biopsies. Loss-of-function experiments in FAPs indicated that a miR-214-3p inhibitor efficiently blocked expression of fibrogenic markers in both basal conditions and following TGFβ1 stimulation. We found that FGFR1 is a functional target of miR-214-3p, preventing the signaling of the anti-fibrotic FGF2 pathway during FAP fibrogenesis. Overall, our work demonstrates that the « FibromiR » miR-214-3p is a key activator of FAP fibrogenesis by modulating the FGF2/FGFR1/TGFβ axis, opening new avenues for the treatment of DMD. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5839290ea56b5e075859d1bcea7fe0eTest https://www.mdpi.com/2073-4409/10/7/1832Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a5839290ea56b5e075859d1bcea7fe0e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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