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Early adipogenesis is repressed through the newly identified FHL2-NFAT5 signaling complex.
Clemente-Olivo, Maria P; Hernández-Quiles, Miguel; Sparrius, Rinske; van der Stoel, Miesje M; Janssen, Vera; Habibe, Jayron J; van den Burg, Janny; Jongejan, Aldo; Alcaraz-Sobrevals, Paula; van Es, Robert; Vos, Harmjan; Kalkhoven, Eric; de Vries, Carlie J M.
Afiliação
  • Clemente-Olivo MP; Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, and Amsterdam Gastroenterology, Endocrinology and Metabolism, University of Amsterdam, Amsterdam, the Netherlands.
  • Hernández-Quiles M; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Sparrius R; Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands.
  • van der Stoel MM; Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands.
  • Janssen V; Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands.
  • Habibe JJ; Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, and Amsterdam Gastroenterology, Endocrinology and Metabolism, University of Amsterdam, Amsterdam, the Netherlands.
  • van den Burg J; Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands.
  • Jongejan A; Amsterdam UMC location University of Amsterdam, Department of Bioinformatics, Amsterdam, the Netherlands.
  • Alcaraz-Sobrevals P; Oncode Institute and Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • van Es R; Oncode Institute and Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Vos H; Oncode Institute and Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Kalkhoven E; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • de Vries CJM; Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, and Amsterdam Gastroenterology, Endocrinology and Metabolism, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: c.j.devries@amster
Cell Signal ; 104: 110587, 2023 04.
Article em En | MEDLINE | ID: mdl-36610523
The LIM-domain-only protein FHL2 is a modulator of signal transduction and has been shown to direct the differentiation of mesenchymal stem cells towards osteoblast and myocyte phenotypes. We hypothesized that FHL2 may simultaneously interfere with the induction of the adipocyte lineage. Therefore, we investigated the role of FHL2 in adipocyte differentiation. For these studies pre-adipocytes isolated from mouse adipose tissue and the 3T3-L1 (pre)adipocyte cell line were applied. We performed FHL2 gain of function and knockdown experiments followed by extensive RNAseq analyses and phenotypic characterization of the cells by oil-red O (ORO) lipid staining. Through affinity-purification mass spectrometry (AP-MS) novel FHL2 interacting proteins were identified. Here we report that FHL2 is expressed in pre-adipocytes and for accurate adipocyte differentiation, this protein needs to be downregulated during the early stages of adipogenesis. More specifically, constitutive overexpression of FHL2 drastically inhibits adipocyte differentiation in 3T3-L1 cells, which was demonstrated by suppressed activation of the adipogenic gene expression program as shown by RNAseq analyses, and diminished lipid accumulation. Analysis of the protein-protein interactions mediating this repressive activity of FHL2 on adipogenesis revealed the interaction of FHL2 with the Nuclear factor of activated T-cells 5 (NFAT5). NFAT5 is an established inhibitor of adipocyte differentiation and its knockdown rescued the inhibitory effect of FHL2 overexpression on 3T3-L1 differentiation, indicating that these proteins act cooperatively. We present a new regulatory function of FHL2 in early adipocyte differentiation and revealed that FHL2-mediated inhibition of pre-adipocyte differentiation is dependent on its interaction with NFAT5. FHL2 expression increases with aging, which may affect mesenchymal stem cell differentiation, more specifically inhibit adipocyte differentiation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adipócitos / Adipogenia Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Signal Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adipócitos / Adipogenia Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Signal Ano de publicação: 2023 Tipo de documento: Article