title: Wnt1 positively regulates CD36 expression via TCF4 and PPAR-γ in macrophages.
abstract: BACKGROUND
  Scavenger receptors including CD36 control the phagocytosis of oxidized low-density lipoprotein and play an important role in macrophage physiology, but the underlying molecular mechanism by which CD36 is regulated in macrophages or during macrophage differentiation from monocytes remains to be determined.
  
  
  METHODS
  Here, we investigated the relationship between Wnt1 and CD36 during macrophage differentiation. CD36 was suppressed following knockdown of Wnt1 by siRNA, while it was increased by ectopic overexpression of Wnt1 in macrophages. Using a β-catenin inhibitor, peroxisome proliferator-activated receptor gamma (PPAR-γ) siRNA, and transcription factor 4 (TCF4) siRNA, we demonstrated that Wnt1 regulates the expression of CD36 through TCF4 and PPAR-γ. Co-immunoprecipitation, chromatin immunoprecipitation, and immunofluorescence experiments showed that β-catenin interacted with PPAR-γ and that PPAR-γ and TCF4 colocalized in the nucleus. Furthermore, Pax3 regulated Wnt1 via binding to the first binding site in the Wnt1 promoter.
  
  
  RESULTS
  Our study demonstrated that during macrophage differentiation from monocytes, Wnt1 promotes CD36 expression via activation of PPAR-γ and TCF4.
  
  
  CONCLUSIONS
  Our findings suggest that Wnt1 plays an important role in macrophage physiology via activation of the canonical Wnt pathway.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.forename: Zewei
authors.initials: Z
authors.lastname: Sun
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Li
authors.forename: Mingjie
authors.initials: M
authors.lastname: Wu
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhao
authors.forename: Houhong
authors.initials: H
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D000072041:PAX3 Transcription Factor; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051761:Paired Box Transcription Factors / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051155:Wnt1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; C495247:WNT1 protein, human; D051155:Wnt1 Protein; D051176:beta Catenin; C099252:oxidized low density lipoprotein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor