PMID: identifiant
de la référence Pubmed : |
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 (22355352)  |
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TGFbeta family members are key mediators in the induction of myofibroblast phenotype of human adipose tissue progenitor cells by macrophages. |
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| auteur(s) : |
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Virginie Bourlier ( ) 1, Coralie Sengenès1, Alexia Zakaroff-Girard1, Pauline Decaunes1, Brigitte Wdziekonski2, Jean Galitzky1, Phi Villageois2, David Esteve1, Patrick Chiotasso3, Christian Dani2, Anne Bouloumié1 |
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| résumé : |
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OBJECTIVE: The present study was undertaken to characterize the remodeling phenotype of human adipose tissue (AT) macrophages (ATM) and to analyze their paracrine effects on AT progenitor cells. RESEARCH DESIGN AND METHODS: The phenotype of ATM, immunoselected from subcutaneous (Sc) AT originating from subjects with wide range of body mass index and from paired biopsies of Sc and omental (Om) AT from obese subjects, was studied by gene expression analysis in the native and activated states. The paracrine effects of ScATM on the phenotype of human ScAT progenitor cells (CD34(+)CD31(-)) were investigated. RESULTS: Two main ATM phenotypes were distinguished based on gene expression profiles. For ScAT-derived ATM, obesity and adipocyte-derived factors favored a pro-fibrotic/remodeling phenotype whereas the OmAT location and hypoxic culture conditions favored a pro-angiogenic phenotype. Treatment of native human ScAT progenitor cells with ScATM-conditioned media induced the appearance of myofibroblast-like cells as shown by expression of both α-SMA and the transcription factor SNAIL, an effect mimicked by TGFβ1 and activinA. Immunohistochemical analyses showed the presence of double positive α-SMA and CD34 cells in the stroma of human ScAT. Moreover, the mRNA levels of SNAIL and SLUG in ScAT progenitor cells were higher in obese compared with lean subjects. CONCLUSIONS: Human ATM exhibit distinct pro-angiogenic and matrix remodeling/fibrotic phenotypes according to the adiposity and the location of AT, that may be related to AT microenvironment including hypoxia and adipokines. Moreover, human ScAT progenitor cells have been identified as target cells for ScATM-derived TGFβ and as a potential source of fibrosis through their induction of myofibroblast-like cells. |
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| domaine : |
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Sciences du Vivant/Génétique
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1932-6203 |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1371/journal.pone.0031274 |
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| journal : |
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| PLoS ONE |
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Public Library of Science |
| ISSN |
1932-6203 |
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| Audience : |
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internationale |
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| date de publication : |
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2012 |
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date de publication
électronique : |
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15/02/2012 |
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| volume : |
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7 |
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| numéro : |
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2 |
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| page, identifiant, ... : |
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e31274 |
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| Descripteur(s) MeSH : |
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Adipose Tissue – Biological Markers – Blotting – Western – Body Composition – Body Mass Index – Cells – Cultured – Gene Expression Profiling – Humans – Immunoenzyme Techniques – Macrophages – Myofibroblasts – Obesity – Oligonucleotide Array Sequence Analysis – Omentum – Phenotype – RNA – Messenger – Real-Time Polymerase Chain Reaction – Reverse Transcriptase Polymerase Chain Reaction – Stem Cells – Subcutaneous Fat – Transforming Growth Factor beta – Adipose Tissue |
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| contrat, financement : |
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This work was supported by INSERM, a grant from ALFEDIAM/Roche Diagnostic, the European Union Commission (Collaborative Project ADAPT (www.adapt-eu.net), Contract No. HEALTH-F2-2008-2011 00) and Clarins SA |
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| Projet Européen : |
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| Acronyme |
HEALTH-F2-2008-2011 00 |
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