The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18.
Identifieur interne : 008707 ( Main/Exploration ); précédent : 008706; suivant : 008708The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18.
Auteurs : Brett M. Hosking [Australie] ; S-C Mary Wang ; Meredith Downes ; Peter Koopman ; George E O. MuscatSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2004.
Descripteurs français
- KwdFr :
- ADN complémentaire (métabolisme), ARN messager (métabolisme), Activation de la transcription, Adhérence cellulaire, Allèles, Animaux, Cellules COS, Délétion de gène, Facteurs de transcription (génétique), Facteurs de transcription (physiologie), Facteurs de transcription SOX-F, Facteurs temps, Fibroblastes (métabolisme), Glutathione transferase (métabolisme), Humains, Lignée cellulaire, Luciferases (métabolisme), Molécule-1 d'adhérence des cellules vasculaires (biosynthèse), Mutagenèse dirigée, Mutation, Mâle, Opossum, Plasmides (métabolisme), Protéines HMG (génétique), Protéines HMG (physiologie), Protéines de fusion recombinantes (métabolisme), RT-PCR, Relation dose-effet des médicaments, Régions promotrices (génétique), Répartition dans les tissus, Sites de fixation, Souris, Souris de lignée C57BL, Techniques de culture cellulaire, Transcription génétique, Transfection.
- MESH :
- biosynthèse : Molécule-1 d'adhérence des cellules vasculaires.
- génétique : Facteurs de transcription, Protéines HMG.
- métabolisme : ADN complémentaire, ARN messager, Fibroblastes, Glutathione transferase, Luciferases, Plasmides, Protéines de fusion recombinantes.
- physiologie : Facteurs de transcription, Protéines HMG.
- Activation de la transcription, Adhérence cellulaire, Allèles, Animaux, Cellules COS, Délétion de gène, Facteurs de transcription SOX-F, Facteurs temps, Humains, Lignée cellulaire, Mutagenèse dirigée, Mutation, Mâle, Opossum, RT-PCR, Relation dose-effet des médicaments, Régions promotrices (génétique), Répartition dans les tissus, Sites de fixation, Souris, Souris de lignée C57BL, Techniques de culture cellulaire, Transcription génétique, Transfection.
English descriptors
- KwdEn :
- Alleles, Animals, Binding Sites, COS Cells, Cell Adhesion, Cell Culture Techniques, Cell Line, DNA, Complementary (metabolism), Dose-Response Relationship, Drug, Fibroblasts (metabolism), Gene Deletion, Glutathione Transferase (metabolism), High Mobility Group Proteins (genetics), High Mobility Group Proteins (physiology), Humans, Luciferases (metabolism), Male, Mice, Mice, Inbred C57BL, Mutagenesis, Site-Directed, Mutation, Opossums, Plasmids (metabolism), Promoter Regions, Genetic, RNA, Messenger (metabolism), Recombinant Fusion Proteins (metabolism), Reverse Transcriptase Polymerase Chain Reaction, SOXF Transcription Factors, Time Factors, Tissue Distribution, Transcription Factors (genetics), Transcription Factors (physiology), Transcription, Genetic, Transcriptional Activation, Transfection, Vascular Cell Adhesion Molecule-1 (biosynthesis).
- MESH :
- chemical , biosynthesis : Vascular Cell Adhesion Molecule-1.
- chemical , genetics : High Mobility Group Proteins, Transcription Factors.
- chemical , metabolism : DNA, Complementary, Glutathione Transferase, Luciferases, RNA, Messenger, Recombinant Fusion Proteins.
- metabolism : Fibroblasts, Plasmids.
- chemical , physiology : High Mobility Group Proteins, Transcription Factors.
- Alleles, Animals, Binding Sites, COS Cells, Cell Adhesion, Cell Culture Techniques, Cell Line, Dose-Response Relationship, Drug, Gene Deletion, Humans, Male, Mice, Mice, Inbred C57BL, Mutagenesis, Site-Directed, Mutation, Opossums, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction, SOXF Transcription Factors, Time Factors, Tissue Distribution, Transcription, Genetic, Transcriptional Activation, Transfection.
Abstract
VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of cross-talk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosis-lymphedema-telangiectasia disorder.
DOI: 10.1074/jbc.M308512200
PubMed: 14634005
Affiliations:
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Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alleles</term>
<term>Animals</term>
<term>Binding Sites</term>
<term>COS Cells</term>
<term>Cell Adhesion</term>
<term>Cell Culture Techniques</term>
<term>Cell Line</term>
<term>DNA, Complementary (metabolism)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Fibroblasts (metabolism)</term>
<term>Gene Deletion</term>
<term>Glutathione Transferase (metabolism)</term>
<term>High Mobility Group Proteins (genetics)</term>
<term>High Mobility Group Proteins (physiology)</term>
<term>Humans</term>
<term>Luciferases (metabolism)</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mutagenesis, Site-Directed</term>
<term>Mutation</term>
<term>Opossums</term>
<term>Plasmids (metabolism)</term>
<term>Promoter Regions, Genetic</term>
<term>RNA, Messenger (metabolism)</term>
<term>Recombinant Fusion Proteins (metabolism)</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>SOXF Transcription Factors</term>
<term>Time Factors</term>
<term>Tissue Distribution</term>
<term>Transcription Factors (genetics)</term>
<term>Transcription Factors (physiology)</term>
<term>Transcription, Genetic</term>
<term>Transcriptional Activation</term>
<term>Transfection</term>
<term>Vascular Cell Adhesion Molecule-1 (biosynthesis)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ADN complémentaire (métabolisme)</term>
<term>ARN messager (métabolisme)</term>
<term>Activation de la transcription</term>
<term>Adhérence cellulaire</term>
<term>Allèles</term>
<term>Animaux</term>
<term>Cellules COS</term>
<term>Délétion de gène</term>
<term>Facteurs de transcription (génétique)</term>
<term>Facteurs de transcription (physiologie)</term>
<term>Facteurs de transcription SOX-F</term>
<term>Facteurs temps</term>
<term>Fibroblastes (métabolisme)</term>
<term>Glutathione transferase (métabolisme)</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Luciferases (métabolisme)</term>
<term>Molécule-1 d'adhérence des cellules vasculaires (biosynthèse)</term>
<term>Mutagenèse dirigée</term>
<term>Mutation</term>
<term>Mâle</term>
<term>Opossum</term>
<term>Plasmides (métabolisme)</term>
<term>Protéines HMG (génétique)</term>
<term>Protéines HMG (physiologie)</term>
<term>Protéines de fusion recombinantes (métabolisme)</term>
<term>RT-PCR</term>
<term>Relation dose-effet des médicaments</term>
<term>Régions promotrices (génétique)</term>
<term>Répartition dans les tissus</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Techniques de culture cellulaire</term>
<term>Transcription génétique</term>
<term>Transfection</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Vascular Cell Adhesion Molecule-1</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>High Mobility Group Proteins</term>
<term>Transcription Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA, Complementary</term>
<term>Glutathione Transferase</term>
<term>Luciferases</term>
<term>RNA, Messenger</term>
<term>Recombinant Fusion Proteins</term>
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<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Molécule-1 d'adhérence des cellules vasculaires</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteurs de transcription</term>
<term>Protéines HMG</term>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Fibroblasts</term>
<term>Plasmids</term>
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<term>ARN messager</term>
<term>Fibroblastes</term>
<term>Glutathione transferase</term>
<term>Luciferases</term>
<term>Plasmides</term>
<term>Protéines de fusion recombinantes</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Facteurs de transcription</term>
<term>Protéines HMG</term>
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<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>High Mobility Group Proteins</term>
<term>Transcription Factors</term>
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<term>Animals</term>
<term>Binding Sites</term>
<term>COS Cells</term>
<term>Cell Adhesion</term>
<term>Cell Culture Techniques</term>
<term>Cell Line</term>
<term>Dose-Response Relationship, Drug</term>
<term>Gene Deletion</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mutagenesis, Site-Directed</term>
<term>Mutation</term>
<term>Opossums</term>
<term>Promoter Regions, Genetic</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>SOXF Transcription Factors</term>
<term>Time Factors</term>
<term>Tissue Distribution</term>
<term>Transcription, Genetic</term>
<term>Transcriptional Activation</term>
<term>Transfection</term>
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<term>Adhérence cellulaire</term>
<term>Allèles</term>
<term>Animaux</term>
<term>Cellules COS</term>
<term>Délétion de gène</term>
<term>Facteurs de transcription SOX-F</term>
<term>Facteurs temps</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Mutagenèse dirigée</term>
<term>Mutation</term>
<term>Mâle</term>
<term>Opossum</term>
<term>RT-PCR</term>
<term>Relation dose-effet des médicaments</term>
<term>Régions promotrices (génétique)</term>
<term>Répartition dans les tissus</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Techniques de culture cellulaire</term>
<term>Transcription génétique</term>
<term>Transfection</term>
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<front><div type="abstract" xml:lang="en">VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of cross-talk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosis-lymphedema-telangiectasia disorder.</div>
</front>
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<affiliations><list><country><li>Australie</li>
</country>
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<tree><noCountry><name sortKey="Downes, Meredith" sort="Downes, Meredith" uniqKey="Downes M" first="Meredith" last="Downes">Meredith Downes</name>
<name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name>
<name sortKey="Muscat, George E O" sort="Muscat, George E O" uniqKey="Muscat G" first="George E O" last="Muscat">George E O. Muscat</name>
<name sortKey="Wang, S C Mary" sort="Wang, S C Mary" uniqKey="Wang S" first="S-C Mary" last="Wang">S-C Mary Wang</name>
</noCountry>
<country name="Australie"><noRegion><name sortKey="Hosking, Brett M" sort="Hosking, Brett M" uniqKey="Hosking B" first="Brett M" last="Hosking">Brett M. Hosking</name>
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