| RRC ID |
41524
|
| 著者 |
Mimuro J, Muramatsu S, Hakamada Y, Mori K, Kikuchi J, Urabe M, Madoiwa S, Ozawa K, Sakata Y.
|
| タイトル |
Recombinant adeno-associated virus vector-transduced vascular endothelial cells express the thrombomodulin transgene under the regulation of enhanced plasminogen activator inhibitor-1 promoter.
|
| ジャーナル |
Gene Ther
|
| Abstract |
We were able to facilitate plasminogen activator inhibitor 1 (PAI-1) promoter activity approximately by 14-fold using an enhancer element. This enhanced PAI-1 promoter has a strong basal activity, comparable to CAG promoter activity, and has a response similar to the PAI-1 promoter with respect to TGFbeta 1 and TNFalpha stimulation. The characteristics of the enhanced PAI-1 promoter are thought to be suited to timely and tissue-specific expression of anticoagulant molecules in the vascular cells. Thus, we developed recombinant adeno-associated virus (rAAV) vectors using the enhanced PAI-1 promoter and were successful in transducing vascular endothelial cells to express the thrombomodulin transgene under the regulation of the enhanced PAI-1 promoter in vitro. Thromobomodulin transgene expression driven by the enhanced PAI-1 promoter in rAAV vector-transduced cultured endothelial cells was between 600- and 1000-fold higher than constitutive thrombomodulin gene expression in cultured human umbilical vein endothelial cells and was up-regulated by TGFbeta1 and TNFalpha stimulation which may down-regulate endogenous thrombomodulin gene expression in endothelial cells. The brain vascular endothelial cells of Mongolian gerbils could also be transduced by the same rAAV vector in vivo. Transduction of endothelial cells by rAAV vectors to express enhanced PAI-1 promoter-driven transgenes may be a useful gene therapy approach for vascular diseases.
|
| 巻・号 |
8(22)
|
| ページ |
1690-7
|
| 公開日 |
2001-11-1
|
| DOI |
10.1038/sj.gt.3301579
|
| PMID |
11892836
|
| MeSH |
Animals
Carotid Artery, Common
Cattle
Cells, Cultured
Dependovirus / genetics*
Endothelium, Vascular / metabolism*
Gene Expression Regulation / drug effects
Genetic Vectors / administration & dosage*
Gerbillinae
Humans
Plasminogen Activator Inhibitor 1 / genetics*
Promoter Regions, Genetic*
Thrombomodulin / genetics*
Transduction, Genetic
Transforming Growth Factor beta / pharmacology
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha / pharmacology
|
| IF |
4.128
|
| 引用数 |
10
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
CPAE(RCB0990) |
