title: GATA-6 is involved in PPARgamma-mediated activation of differentiated phenotype in human vascular smooth muscle cells.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily involved in the growth and differentiation of many cell types. Although the activation of PPARgamma in human vascular smooth muscle cells (VSMCs) inhibits the growth of these cells, the precise mechanism of this effect is unknown. PPARgamma-mediated growth inhibition of VSMCs is associated with the induction of the differentiated phenotype. A zinc finger transcription factor, GATA-6, has been implicated in the maintenance of the differentiated phenotype in VSMCs.
  
  
  RESULTS
  The administration of 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), a naturally occurring PPARgamma ligand, and troglitazone, a thiazolidinedione derivative, induced the expression of smooth muscle myosin heavy chain and smooth muscle alpha-actin, highly specific markers for differentiated VSMCs. Stimulation of proliferative VSMCs with PPARgamma ligands also increased the activity of the transfected wild-type smooth muscle myosin heavy chain promoter but not that of the mutant promoter, in which a GATA-6 binding site was mutated. Compatible with the role of GATA-6, both 15d-PGJ2 and troglitazone upregulated the DNA binding activity of GATA-6 in proliferative VSMCs.
  
  
  CONCLUSIONS
  The activation of PPARgamma-dependent pathways induces the differentiated phenotype in proliferative VSMCs, and this induction is mediated, in part, through a GATA-6-dependent transcriptional mechanism.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Abe
authors.forename: Koji
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morimoto
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Yanazume
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Kawamura
authors.forename: Maretoshi
authors.initials: M
authors.lastname: Hirai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
mesh_terms: D000199:Actins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D050993:GATA6 Transcription Factor; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010641:Phenotype; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D000077288:Troglitazone
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000199:Actins; D002839:Chromans; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; C408902:MHC binding peptide; D009842:Oligopeptides; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone; D015230:Prostaglandin D2; D004121:Dimethyl Sulfoxide