Wnt1 positively regulates CD36 expression via TCF4 and PPAR-γ in macrophages

Shuai Wang; Zewei Sun; Xi Zhang; Zhenwei Li; Mingjie Wu; Wenting Zhao; Houhong Wang; Ting Chen; Hui Yan; Jianhua Zhu

doi:10.1159/000373951

Wnt1 positively regulates CD36 expression via TCF4 and PPAR-γ in macrophages

Cell Physiol Biochem. 2015;35(4):1289-302. doi: 10.1159/000373951. Epub 2015 Feb 11.

Authors

Shuai Wang¹, Zewei Sun, Xi Zhang, Zhenwei Li, Mingjie Wu, Wenting Zhao, Houhong Wang, Ting Chen, Hui Yan, Jianhua Zhu

Affiliation

¹ Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

PMID: 25721714
DOI: 10.1159/000373951

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / antagonists & inhibitors
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
Binding Sites
CD36 Antigens / genetics
CD36 Antigens / metabolism*
Cell Differentiation / drug effects
Cells, Cultured
Chromatin Immunoprecipitation
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Humans
Lipoproteins, LDL / pharmacology
Macrophages / cytology
Macrophages / metabolism*
Monocytes / cytology
PAX3 Transcription Factor
PPAR gamma / antagonists & inhibitors
PPAR gamma / genetics
PPAR gamma / metabolism*
Paired Box Transcription Factors / chemistry
Paired Box Transcription Factors / metabolism
Promoter Regions, Genetic
Protein Binding
RNA Interference
Transcription Factor 4
Transcription Factors / antagonists & inhibitors
Transcription Factors / genetics
Transcription Factors / metabolism*
Up-Regulation / drug effects
Wnt1 Protein / antagonists & inhibitors
Wnt1 Protein / genetics
Wnt1 Protein / metabolism*
beta Catenin / antagonists & inhibitors
beta Catenin / metabolism

Substances

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
CD36 Antigens
Lipoproteins, LDL
PAX3 Transcription Factor
PAX3 protein, human
PPAR gamma
Paired Box Transcription Factors
TCF4 protein, human
Transcription Factor 4
Transcription Factors
WNT1 protein, human
Wnt1 Protein
beta Catenin
oxidized low density lipoprotein
Granulocyte-Macrophage Colony-Stimulating Factor