Tài liệu Báo cáo khoa học: ¨ Induction of Kruppel-like factor 4 by high-density lipoproteins

Induction of Kru¨ ppel-like factor 4 by high-density

lipoproteins promotes the expression of scavenger

receptor class B type I

Tao Yang1,2,3,*, Caihong Chen4,*, Bin Zhang1

, He Huang1

, Ganqiu Wu1

, Jianguo Wen1 and

Junwen Liu1

1 Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China

2 College of Chemistry and Bioengineering, Changsha University of Science and Technology, Hunan, China

3 College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, China

4 School of Science, Central South University of Forestry and Technology, Changsha, Hunan, China

Introduction

Atherosclerosis is a chronic inflammatory response in

the walls of arteries, in large part due to the accumula￾tion of macrophages and white blood cells, and pro￾moted by low-density lipoproteins (LDL) without

adequate removal of fats and cholesterol from the

macrophages by functional high-density lipoproteins

(HDL). Vascular smooth muscle cells (VSMCs), endo￾thelial cells and macrophages are the three predomi￾nant cell types involved in atherosclerosis, and the

proliferation, migration, differentiation and activation

of cells are always highlights for researchers.

Kru¨ppel-like factor 4 (KLF4) was first identified in

the epithelial lining of the gut and skin, and subse￾quent studies have shown it to play a role in the regu￾lation of cellular growth and differentiation in these

tissues [1]. Recently, it has been shown that KLF4

Keywords

atherosclerosis; gene regulation; high￾density lipoproteins; Kru¨ppel-like factor 4;

scavenger receptor class B type I

Correspondence

J. Liu, Department of Histology and

Embryology, School of Basic Medical

Sciences, Central South University,

Changsha, Hunan 410013, China

Fax: 86 731 82650400

Tel: 86 731 82650436

E-mail: [email protected]

*These authors contributed equally to this

work

(Received 27 April 2010, revised 12 June

2010, accepted 14 July 2010)

doi:10.1111/j.1742-4658.2010.07779.x

Kru¨ppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger￾containing transcription factor. In the present study, peripheral blood

mononuclear cells and phorbol 12-myristate 13-acetate-differentiated THP￾1 cells were treated with oxidized low-density lipoproteins and high-density

lipoproteins to determine the expression of KLF4 and scavenger receptor

class B type I (SR-BI). A full-length cDNA of KLF4 or short interference

RNA against KLF4 was transfected into THP-1 cells, and the subsequent

expressions of SR-BI were analysed by real-time PCR and western blot.

The binding and transcriptional activities of KLF4 to the SR-BI promoter

were detected by electrophoretic mobility shift assay, chromatin immuno￾precipitation assay and luciferase reporter assay. The results showed that

induction of KLF4 by high-density lipoproteins could promote the expres￾sion of SR-BI, resulting from the binding to putative KLF4 binding

element on the promoter of SR-BI. All results indicate a potential function

of KLF4 in the pathogenesis of atherosclerosis through the regulation

effect on atherosclerotic-related genes.

Abbreviations

ChIP, chromatin immunoprecipitation; EMSA, electrophoretic mobility shift assay; HDL, high-density lipoproteins; hSR-BI, human scavenger

receptor class B type I; IFN, interferon; KLF4, Kru¨ppel-like factor 4; LDL, low-density lipoproteins; LPS, lipopolysaccharide; oxLDL, oxidized

low-density lipoprotein; PBMC, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; PMA, phorbol 12-myristate 13-acetate;

siRNA, short interference RNA; SR-BI, scavenger receptor class B type I; TESS, transcription element search system; VSMC, vascular

smooth muscle cell.

3780 FEBS Journal 277 (2010) 3780–3788 ª 2010 The Authors Journal compilation ª 2010 FEBS