title: Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor gamma during bone morphogenetic protein 2-induced adipogenesis.
abstract: Bone morphogenetic protein 2 (BMP2) promotes the differentiation of undifferentiated mesenchymal cells into adipocytes. To investigate the molecular mechanisms that regulate this differentiation process, we studied the relationship between BMP2 signaling and peroxisome proliferator-activating receptor gamma (PPARgamma) during adipogenesis of mesenchymal cells by using pluripotent mesenchymal cell line C3H10T1/2. In C3H10T1/2 cells, BMP2 induced expression of PPARgamma along with adipogenesis. Overexpression of Smad6, a natural antagonist for Smad1, blocked PPARgamma expression and adipocytic differentiation induced by BMP2. Overexpression of dominant-negative PPARgamma also diminished adipocytic differentiation of C3H10T1/2 cells, suggesting the central role of PPARgamma in BMP2-induced adipocytic differentiation. Specific inhibitors for p38 kinase inhibited BMP2-induced adipocytic differentiation and transcriptional activation of PPARgamma, whereas overexpression of Smad6 had no effect on transcriptional activity of PPARgamma. Furthermore, activation of p38 kinase by overexpression of TAK1 and TAB1, without affecting PPARgamma expression, led the up-regulation of transcriptional activity of PPARgamma. These results suggest that both Smad and p38 kinase signaling are concomitantly activated and responsible for BMP2-induced adipocytic differentiation by inducing and up-regulating PPARgamma, respectively. Thus, BMP2 controls adipocytic differentiation by using two distinct signaling pathways that play differential roles in this process in C3H10T1/2 cells.
authors.affiliation: Department of Biochemistry, Osaka University Graduate School/Faculty of Dentistry, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hata
authors.forename: Riko
authors.initials: R
authors.lastname: Nishimura
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Ikeda
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamashita
authors.forename: Takuma
authors.initials: T
authors.lastname: Matsubara
authors.forename: Takashi
authors.initials: T
authors.lastname: Nokubi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D015151:Immunoblotting; D051379:Mice; D008809:Mice, Inbred C3H; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011233:Precipitin Tests; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins; D051898:Smad1 Protein; D051905:Smad6 Protein; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D051785:Smad Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051905:Smad6 Protein; C497803:Smad6 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases