title: IER3 Promotes Expansion of Adipose Progenitor Cells in Response to Changes in Distinct Microenvironmental Effectors.
abstract: Adipose tissue expansion is well-orchestrated to fulfill the energy demand. It results from adipocyte hypertrophy and hyperplasia due to adipose progenitor cell (APC) expansion and differentiation. Chronic low grade inflammation and hypoxia take place in obese adipose tissue microenvironment. Both of these events were shown to impact the APC pool by promoting increased self-renewal along with a decrease in the APC differentiation potential. However, no common target has been identified so far. Here we show that the immediate early response 3 gene (IER3) is preferentially expressed in APCs and is essential for APC proliferation and self-renewal. Experiments based on RNA interference revealed that impairing IER3 expression altered cell proliferation through ERK1/2 phosphorylation and clonogenicity. IER3 expression was induced by Activin A, which plays a crucial role in adipocyte differentiation as well as by a decrease in oxygen tension through HIF1-induced transcriptional activation. Interestingly, high levels of IER3 were detected in native APCs (CD34+/CD31- cells) isolated from obese patients and conditioned media from obese adipose tissue-macrophages stimulated its expression. Overall, these results indicate that IER3 is a key player in expanding the pool of APC while highlighting the role of distinct effectors found in an obese microenvironment in this process.
authors.affiliation: CNRS UMR 7277, Nice, France.|University of Nice-Sophia Antipolis, Nice, France.|INSERM UMR 1091, iBV, Nice, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ravaud
authors.affiliation: Team 1, INSERM UMR1048, Institute of Cardiovascular and Metabolic Diseases, University of Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: David
authors.initials: D
authors.lastname: Esteve
authors.affiliation: CNRS UMR 7277, Nice, France.|University of Nice-Sophia Antipolis, Nice, France.|INSERM UMR 1091, iBV, Nice, France.
authors.forename: Phi
authors.initials: P
authors.lastname: Villageois
authors.affiliation: Team 1, INSERM UMR1048, Institute of Cardiovascular and Metabolic Diseases, University of Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bouloumie
authors.affiliation: CNRS UMR 7277, Nice, France.|University of Nice-Sophia Antipolis, Nice, France.|INSERM UMR 1091, iBV, Nice, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Dani
authors.affiliation: CNRS UMR 7277, Nice, France.|University of Nice-Sophia Antipolis, Nice, France.|INSERM UMR 1091, iBV, Nice, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Ladoux
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D008565:Membrane Proteins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Activin A; Adipose tissue; Hyperplasia; Immediate early genes; Inflammation; Mesenchymal stem cells; Oxygen