Genomic Organization and Regulation of Expression of the Lectin-like Oxidized Low-density Lipoprotein Receptor (LOX-1) Gene*
- From the Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo 112-0015, the§Department of Biological Sciences, Tokyo Institute of Technology, Yokohama, Kanagawa 226-8503, and the ¶Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
Abstract
Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a recently identified receptor for oxidized low-density lipoprotein, one of the major atherogenic substances. Although LOX-1 was reported to be expressed abundantly in endothelial cells, including atheromatous lesions, the regulation of LOX-1 gene has not yet been clarified. In the present study, we isolated the rat LOX-1 gene and investigated the regulation of gene expression. The rat LOX-1 gene was encoded by a single copy gene spanning over 19 kilobases and consisted of eight exons. Exon boundaries correlated well with the functional domain boundaries of the receptor protein. The promoter region contained putative TATA and CAAT boxes and multiple cis-elements such as NF-κB, AP-1 and AP-2 sites, and a shear stress response element. Northern blot analysis revealed that LOX-1 gene expression was up-regulated 9-fold by shear stress, 21-fold by lipopolysaccharide, and 4-fold by tumor necrosis factor-α, in cultured vascular endothelial cells. LOX-1 was also expressed in macrophages but not in vascular smooth muscle cells. These data provide important information for elucidating the molecular mechanisms of LOX-1 gene regulation and suggest a role for LOX-1 in the pathophysiology of atherosclerotic cardiovascular disease.
Footnotes
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↵* This work was supported in part by a grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, Japanese Heart Foundation Grant for Research on Hypertension and Vascular Metabolism, Research Grants from the SRF, and by the Life Insurance Association of Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AB018097–AB018104.
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↵‡ To whom all correspondence should be addressed: Fourth Dept. of Internal Medicine, University of Tokyo School of Medicine, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo 112-8688, Japan. Tel.: 81-3-3943-1151; Fax: 81-3-3943-3102; E-mail: mnagase-tky{at}umin.u-tokyo.ac.jp.
- Abbreviations:
- OxLDL
-
oxidized low-density lipoprotein
- LOX-1
-
lectin-like OxLDL receptor
- LPS
-
lipopolysaccharides
- TNF
-
tumor necrosis factor
- bp
-
base pair(s)
- PCR
-
polymerase chain reaction
- EC(s)
-
endothelial cell(s)
- GAPDH
-
glyceraldehyde-3-phosphate dehydrogenase
- SSRE
-
shear stress response element
- kb
-
kilobase(s).
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- Received August 24, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
