title: TGFbeta family members are key mediators in the induction of myofibroblast phenotype of human adipose tissue progenitor cells by macrophages.
abstract: 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.
  
  
  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.
authors.affiliation: UMR1048, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III Paul-Sabatier, Toulouse, France. virginie.bourlier@inserm.fr
authors.forename: Virginie
authors.initials: V
authors.lastname: Bourlier
authors.forename: Coralie
authors.initials: C
authors.lastname: Sengenès
authors.forename: Alexia
authors.initials: A
authors.lastname: Zakaroff-Girard
authors.forename: Pauline
authors.initials: P
authors.lastname: Decaunes
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wdziekonski
authors.forename: Jean
authors.initials: J
authors.lastname: Galitzky
authors.forename: Phi
authors.initials: P
authors.lastname: Villageois
authors.forename: David
authors.initials: D
authors.lastname: Esteve
authors.forename: Patrick
authors.initials: P
authors.lastname: Chiotasso
authors.forename: Christian
authors.initials: C
authors.lastname: Dani
authors.forename: Anne
authors.initials: A
authors.lastname: Bouloumié
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001823:Body Composition; D015992:Body Mass Index; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009852:Omentum / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000166:cytology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta