title: Angiopoietin-like protein 2, a chronic inflammatory mediator, is a new target induced by TGF-β1 through a Smad3-dependent mechanism.
abstract: Angiopoietin-like protein 2 (Angptl2) levels are increased by obesity and obesity-related pathological conditions, and it is considered to be an important adipocyte-derived inflammatory mediator. In contrast, the multifunctional cytokine TGF-β1 has been reported to be augmented in obesity of rodents and humans, but inhibits adipocyte differentiation in vitro. Here we demonstrate that TGF-β1 induces expression of the Angptl2 gene through a Smad3-dependent pathway in RAW264.7 macrophage cells, primary peritoneal macrophages, and differentiated 3T3-L1 adipocytes. Transcriptional induction of the Angptl2 gene by TGF-β1 was dependent on the Smad3 protein which binds to the Smad Binding Element (SBE) region located on the Angptl2 promoter. Macrophages with Smad3 knocked down by small interfering RNA showed reduction of TGF-β1-induced Angptl2 expression. These findings may provide insight into the molecular mechanisms of the increased expression of Angptl2 and TGF-β1 in obesity.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jun Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Joon-Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Ryan Dennis
authors.initials: RD
authors.lastname: Martinus
authors.forename: Seok Hee
authors.initials: SH
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002908:Chronic Disease; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D007249:Inflammation / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1