The Transcription Factor SOX18 Regulates the Expression of Matrix Metalloproteinase 7 and Guidance Molecules in Human Endothelial Cells
Identifieur interne : 003E18 ( Main/Exploration ); précédent : 003E17; suivant : 003E19The Transcription Factor SOX18 Regulates the Expression of Matrix Metalloproteinase 7 and Guidance Molecules in Human Endothelial Cells
Auteurs : Martina Hoeth [Autriche] ; Heide Niederleithner [Autriche] ; Renate Hofer-Warbinek [Autriche] ; Martin Bilban [Autriche] ; Herbert Mayer [Autriche] ; Ulrike Resch [Autriche] ; Christof Lemberger [Autriche] ; Oswald Wagner [Autriche] ; Erhard Hofer [Autriche] ; Peter Petzelbauer [Autriche] ; Rainer De Martin [Autriche]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
Mutations in the transcription factor SOX18 are responsible for specific cardiovascular defects in humans and mice. In order to gain insight into the molecular basis of its action, we identified target genes of SOX18 and analyzed one,
SOX18 was expressed in HUVEC using a recombinant adenoviral vector and the altered gene expression profile was analyzed using microarrays. Expression of several regulated candidate SOX18 target genes was verified by real-time PCR. Knock-down of SOX18 using RNA interference was then used to confirm the effect of the transcription factor on selected genes that included the guidance molecules ephrin B2 and semaphorin 3G. One gene,
The identification of
Url:
DOI: 10.1371/journal.pone.0030982
PubMed: 22292085
PubMed Central: 3264645
Affiliations:
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Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22292085</idno><idno type="pmc">3264645</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264645</idno><idno type="RBID">PMC:3264645</idno><idno type="doi">10.1371/journal.pone.0030982</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">004525</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004525</idno><idno type="wicri:Area/Pmc/Curation">004524</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">004524</idno><idno 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xml:lang="fr">Autriche</country><wicri:regionArea>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Niederleithner, Heide" sort="Niederleithner, Heide" uniqKey="Niederleithner H" first="Heide" last="Niederleithner">Heide Niederleithner</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Dermatology, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Dermatology, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Hofer Warbinek, Renate" sort="Hofer Warbinek, Renate" uniqKey="Hofer Warbinek R" first="Renate" last="Hofer-Warbinek">Renate Hofer-Warbinek</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Bilban, Martin" sort="Bilban, Martin" uniqKey="Bilban M" first="Martin" last="Bilban">Martin Bilban</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Mayer, Herbert" sort="Mayer, Herbert" uniqKey="Mayer H" first="Herbert" last="Mayer">Herbert Mayer</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Resch, Ulrike" sort="Resch, Ulrike" uniqKey="Resch U" first="Ulrike" last="Resch">Ulrike Resch</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Lemberger, Christof" sort="Lemberger, Christof" uniqKey="Lemberger C" first="Christof" last="Lemberger">Christof Lemberger</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Wagner, Oswald" sort="Wagner, Oswald" uniqKey="Wagner O" first="Oswald" last="Wagner">Oswald Wagner</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Hofer, Erhard" sort="Hofer, Erhard" uniqKey="Hofer E" first="Erhard" last="Hofer">Erhard Hofer</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Petzelbauer, Peter" sort="Petzelbauer, Peter" uniqKey="Petzelbauer P" first="Peter" last="Petzelbauer">Peter Petzelbauer</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Dermatology, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Dermatology, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="De Martin, Rainer" sort="De Martin, Rainer" uniqKey="De Martin R" first="Rainer" last="De Martin">Rainer De Martin</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Mutations in the transcription factor SOX18 are responsible for specific cardiovascular defects in humans and mice. In order to gain insight into the molecular basis of its action, we identified target genes of SOX18 and analyzed one, <italic>MMP7</italic>, in detail.</p></sec><sec><title>Methodology/Principal Findings</title><p>SOX18 was expressed in HUVEC using a recombinant adenoviral vector and the altered gene expression profile was analyzed using microarrays. Expression of several regulated candidate SOX18 target genes was verified by real-time PCR. Knock-down of SOX18 using RNA interference was then used to confirm the effect of the transcription factor on selected genes that included the guidance molecules ephrin B2 and semaphorin 3G. One gene, <italic>MMP7</italic>, was chosen for further analysis, including detailed promoter studies using reporter gene assays, electrophoretic mobility shift analysis and chromatin-immunoprecipitation, revealing that it responds directly to SOX18. Immunohistochemical analysis demonstrated the co-expression of SOX18 and MMP7 in blood vessels of human skin.</p></sec><sec><title>Conclusions/Significance</title><p>The identification of <italic>MMP7</italic> as a direct SOX18 target gene as well as other potential candidates including guidance molecules provides a molecular basis for the proposed function of this transcription factor in the regulation of vessel formation.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Irrthum, A" uniqKey="Irrthum A">A Irrthum</name></author><author><name sortKey="Devriendt, K" uniqKey="Devriendt K">K Devriendt</name></author><author><name sortKey="Chitayat, D" uniqKey="Chitayat D">D Chitayat</name></author><author><name sortKey="Matthijs, G" uniqKey="Matthijs G">G Matthijs</name></author><author><name sortKey="Glade, C" uniqKey="Glade C">C Glade</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Francois, 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uniqKey="Augustin H">HG Augustin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taniguchi, M" uniqKey="Taniguchi M">M Taniguchi</name></author><author><name sortKey="Masuda, T" uniqKey="Masuda T">T Masuda</name></author><author><name sortKey="Fukaya, M" uniqKey="Fukaya M">M Fukaya</name></author><author><name sortKey="Kataoka, H" uniqKey="Kataoka H">H Kataoka</name></author><author><name sortKey="Mishina, M" uniqKey="Mishina M">M Mishina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neufeld, G" uniqKey="Neufeld G">G Neufeld</name></author><author><name sortKey="Lange, T" uniqKey="Lange T">T Lange</name></author><author><name sortKey="Varshavsky, A" uniqKey="Varshavsky A">A Varshavsky</name></author><author><name sortKey="Kessler, O" uniqKey="Kessler O">O Kessler</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Autriche</li></country><region><li>Vienne (Autriche)</li></region><settlement><li>Vienne (Autriche)</li></settlement></list><tree><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Hoeth, Martina" sort="Hoeth, Martina" uniqKey="Hoeth M" first="Martina" last="Hoeth">Martina Hoeth</name></region><name sortKey="Bilban, Martin" sort="Bilban, Martin" uniqKey="Bilban M" first="Martin" last="Bilban">Martin Bilban</name><name sortKey="De Martin, Rainer" sort="De Martin, Rainer" uniqKey="De Martin R" first="Rainer" last="De Martin">Rainer De Martin</name><name sortKey="Hofer Warbinek, Renate" sort="Hofer Warbinek, Renate" uniqKey="Hofer Warbinek R" first="Renate" last="Hofer-Warbinek">Renate Hofer-Warbinek</name><name sortKey="Hofer, Erhard" sort="Hofer, Erhard" uniqKey="Hofer E" first="Erhard" last="Hofer">Erhard Hofer</name><name sortKey="Lemberger, Christof" sort="Lemberger, Christof" uniqKey="Lemberger C" first="Christof" last="Lemberger">Christof Lemberger</name><name sortKey="Mayer, Herbert" sort="Mayer, Herbert" uniqKey="Mayer H" first="Herbert" last="Mayer">Herbert Mayer</name><name sortKey="Niederleithner, Heide" sort="Niederleithner, Heide" uniqKey="Niederleithner H" first="Heide" last="Niederleithner">Heide Niederleithner</name><name sortKey="Petzelbauer, Peter" sort="Petzelbauer, Peter" uniqKey="Petzelbauer P" first="Peter" last="Petzelbauer">Peter Petzelbauer</name><name sortKey="Resch, Ulrike" sort="Resch, Ulrike" uniqKey="Resch U" first="Ulrike" last="Resch">Ulrike Resch</name><name sortKey="Wagner, Oswald" sort="Wagner, Oswald" uniqKey="Wagner O" first="Oswald" last="Wagner">Oswald Wagner</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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