Upregulation of decorin by FXR in vascular smooth muscle cells.
Decorin is a member of the family of small leucine-rich proteoglycans that are present in blood vessels and synthesized by vascular smooth muscle cells (VSMCs). Decorin plays complex roles in both normal vascular physiology and the pathogenesis of various types of vascular disorders. However, the mechanisms of regulation of decorin expression in vasculature are not clearly understood. Particularly little information is available about a role of nuclear receptors in the regulation of decorin expression. In the present study, we report that activation of vascular FXR by a specific ligand resulted in upregulation of decorin at the levels of both mRNA and protein. FXR appears to induce decorin expression at a transcriptional level because (1) upregulation of decorin mRNA expression was abolished by the treatment of a transcription inhibitor, actinomycin D; and (2) decorin promoter activity was significantly increased by activation of FXR. Functional analysis of human decorin promoter identified an imperfect inverted repeat DNA motif, IR8 (-2313TGGTCAtagtgtcaTGACCT-2294), as a likely FXR-responsive element that is involved in decorin regulation.
Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 639 Salk Hall, Pittsburgh, PA 15261, USA.
Fengtian
F
He
Qiuhong
Q
Zhang
Ramalinga
R
Kuruba
Xiang
X
Gao
Jiang
J
Li
Yong
Y
Li
Wei
W
Gong
Yu
Y
Jiang
Wen
W
Xie
Song
S
Li
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000819:agonists / Q000378:metabolism*; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D020218:Response Elements / Q000187:drug effects; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism*; D015854:Up-Regulation; D000099150:Receptor, Farnesoid X-Activated
D004268:DNA-Binding Proteins; D058575:Decorin; D016326:Extracellular Matrix Proteins; D007555:Isoxazoles; D011509:Proteoglycans; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C546878:DCN protein, human; C412815:GW 4064