VE-cadherin post-translational modifications : from molecular mechanisms to clinical applications : from molecular mechanisms to clinical applications
Identifieur interne : 000142 ( Main/Exploration ); précédent : 000141; suivant : 000143VE-cadherin post-translational modifications : from molecular mechanisms to clinical applications : from molecular mechanisms to clinical applications
Auteurs : Adama Sidibe [France]Source :
Descripteurs français
English descriptors
Abstract
The vascular endothelium barrier function is influenced by vascular endothelial cadherin (VE-cadherin) modifications such as its cytoplasmic tail tyrosine phosphorylation and its ecto-domain cleavage (sVE). The work reported herein was divided into two parts: 1- Study of VE-cadherin modifications and the mechanisms underlying these ones in the rheumatoid arthritis context. This work demonstrated that VE-cadherin is a target of TNFα, a highly important cytokine in rheumatoid arthritis (RA) pathogenesis. We found TNFα to induce sVE shedding in a Src kinase dependent manner, suggesting the involvement of phosphorylation mechanism in this process. In addition, this VE-cadherin cleavage requires matrix metalloproteinase activities such as that of MMP-2. Applying these fundamental data to clinical study showed that sVE was detected in sera of 63 RA patients and its titer was correlated with the disease activity. This finding suggests an obvious interest for assaying sVE in RA therapies. 2- Study of VE-cadherin tyrosine phosphorylation in a context of hormones-regulated angiogenesis during mouse estrous cycle. The results showed VE-cadherin phosphorylation at Y685 that was regulated along mouse estrous cycle allowing to proposing mouse estrous cycle as a physiological model for studying VE-cadherin phosphorylation in vivo. The analysis of VE-cadherin Y685F knock-in mice (VE-Y685F) showed that these mice exhibit a higher vascular permeability in uterus and ovaries and the skin small capillaries compared to wild-type animals. Moreover, VE-Y685F mice presented higher levels of soluble VE-cadherin compared to wild-type counterparts in two induced arthritis model. Altogether, sVE and VE-cadherin phosphorylation present an array of interests for RA therapies as well as developing new therapeutic tools in RA and other vascular diseases.
Url:
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Hal, to step Corpus: 000182
- to stream Hal, to step Curation: 000182
- to stream Hal, to step Checkpoint: 000110
- to stream Main, to step Merge: 000142
- to stream Main, to step Curation: 000142
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">VE-cadherin post-translational modifications : from molecular mechanisms to clinical applications : from molecular mechanisms to clinical applications</title>
<title xml:lang="fr">Modifications post-traductionnelles de la VE-cadhérine : des mécanismes moléculaires aux applications cliniques</title>
<author><name sortKey="Sidibe, Adama" sort="Sidibe, Adama" uniqKey="Sidibe A" first="Adama" last="Sidibe">Adama Sidibe</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-139730" status="VALID"> <idno type="RNSR">201119439L</idno>
<orgName>Biologie du Cancer et de l'Infection</orgName>
<orgName type="acronym">BCI - UMR S1036</orgName>
<desc> <address> <addrLine>BIOLOGIE DU CANCER ET DE L'INFECTION : DES MÉCANISMES MOLÉCULAIRES AUX APPLICATIONS TECHNOLOGIQUES17 rue des martyrs 38054 Grenoble cedex 9</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation> <relation name="DRF/BIG" active="#struct-300016" type="direct"></relation>
<relation name="U1036" active="#struct-303623" type="direct"></relation>
<relation active="#struct-445543" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="DRF/BIG" active="#struct-300016" type="direct"><org type="institution" xml:id="struct-300016" status="VALID"> <orgName>Commissariat à l'énergie atomique et aux énergies alternatives</orgName>
<orgName type="acronym">CEA</orgName>
<desc> <address> <addrLine>Centre de SaclayCentre de GrenobleCentre de Cadaracheetc</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.cea.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="U1036" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno>
<orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
<orgName type="acronym">INSERM</orgName>
<desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.inserm.fr</ref>
</desc>
</org>
</tutelle>
<tutelle active="#struct-445543" type="direct"><org type="institution" xml:id="struct-445543" status="VALID"> <idno type="IdRef">188399275</idno>
<orgName>Université Grenoble Alpes</orgName>
<orgName type="acronym">UGA</orgName>
<date type="start">2016-01-01</date>
<desc> <address> <addrLine>CS 40700 - 38058 Grenoble cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-grenoble-alpes.fr</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
<placeName><settlement type="city">Grenoble</settlement>
<region type="region" nuts="2">Auvergne-Rhône-Alpes</region>
<region type="old region" nuts="2">Rhône-Alpes</region>
</placeName>
<orgName type="university">Université Grenoble-Alpes</orgName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">HAL</idno>
<idno type="RBID">Hal:tel-00819876</idno>
<idno type="halId">tel-00819876</idno>
<idno type="halUri">https://tel.archives-ouvertes.fr/tel-00819876</idno>
<idno type="url">https://tel.archives-ouvertes.fr/tel-00819876</idno>
<date when="2012-12-14">2012-12-14</date>
<idno type="wicri:Area/Hal/Corpus">000182</idno>
<idno type="wicri:Area/Hal/Curation">000182</idno>
<idno type="wicri:Area/Hal/Checkpoint">000110</idno>
<idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">000110</idno>
<idno type="wicri:Area/Main/Merge">000142</idno>
<idno type="wicri:Area/Main/Curation">000142</idno>
<idno type="wicri:Area/Main/Exploration">000142</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">VE-cadherin post-translational modifications : from molecular mechanisms to clinical applications : from molecular mechanisms to clinical applications</title>
<title xml:lang="fr">Modifications post-traductionnelles de la VE-cadhérine : des mécanismes moléculaires aux applications cliniques</title>
<author><name sortKey="Sidibe, Adama" sort="Sidibe, Adama" uniqKey="Sidibe A" first="Adama" last="Sidibe">Adama Sidibe</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-139730" status="VALID"> <idno type="RNSR">201119439L</idno>
<orgName>Biologie du Cancer et de l'Infection</orgName>
<orgName type="acronym">BCI - UMR S1036</orgName>
<desc> <address> <addrLine>BIOLOGIE DU CANCER ET DE L'INFECTION : DES MÉCANISMES MOLÉCULAIRES AUX APPLICATIONS TECHNOLOGIQUES17 rue des martyrs 38054 Grenoble cedex 9</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation> <relation name="DRF/BIG" active="#struct-300016" type="direct"></relation>
<relation name="U1036" active="#struct-303623" type="direct"></relation>
<relation active="#struct-445543" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="DRF/BIG" active="#struct-300016" type="direct"><org type="institution" xml:id="struct-300016" status="VALID"> <orgName>Commissariat à l'énergie atomique et aux énergies alternatives</orgName>
<orgName type="acronym">CEA</orgName>
<desc> <address> <addrLine>Centre de SaclayCentre de GrenobleCentre de Cadaracheetc</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.cea.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="U1036" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno>
<orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
<orgName type="acronym">INSERM</orgName>
<desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.inserm.fr</ref>
</desc>
</org>
</tutelle>
<tutelle active="#struct-445543" type="direct"><org type="institution" xml:id="struct-445543" status="VALID"> <idno type="IdRef">188399275</idno>
<orgName>Université Grenoble Alpes</orgName>
<orgName type="acronym">UGA</orgName>
<date type="start">2016-01-01</date>
<desc> <address> <addrLine>CS 40700 - 38058 Grenoble cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-grenoble-alpes.fr</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
<placeName><settlement type="city">Grenoble</settlement>
<region type="region" nuts="2">Auvergne-Rhône-Alpes</region>
<region type="old region" nuts="2">Rhône-Alpes</region>
</placeName>
<orgName type="university">Université Grenoble-Alpes</orgName>
</affiliation>
</author>
</analytic>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>Angiogenesis</term>
<term>Phosphorylation</term>
<term>Rhumatoid arthritis</term>
<term>VE-cadherin</term>
<term>Vascular endothelium</term>
</keywords>
<keywords scheme="mix" xml:lang="fr"><term>Angiogenèse</term>
<term>Endothélium vasculaire</term>
<term>Polyarthrite rhumatoide</term>
<term>Tyrosine kinase</term>
<term>VE-cadhérine</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The vascular endothelium barrier function is influenced by vascular endothelial cadherin (VE-cadherin) modifications such as its cytoplasmic tail tyrosine phosphorylation and its ecto-domain cleavage (sVE). The work reported herein was divided into two parts: 1- Study of VE-cadherin modifications and the mechanisms underlying these ones in the rheumatoid arthritis context. This work demonstrated that VE-cadherin is a target of TNFα, a highly important cytokine in rheumatoid arthritis (RA) pathogenesis. We found TNFα to induce sVE shedding in a Src kinase dependent manner, suggesting the involvement of phosphorylation mechanism in this process. In addition, this VE-cadherin cleavage requires matrix metalloproteinase activities such as that of MMP-2. Applying these fundamental data to clinical study showed that sVE was detected in sera of 63 RA patients and its titer was correlated with the disease activity. This finding suggests an obvious interest for assaying sVE in RA therapies. 2- Study of VE-cadherin tyrosine phosphorylation in a context of hormones-regulated angiogenesis during mouse estrous cycle. The results showed VE-cadherin phosphorylation at Y685 that was regulated along mouse estrous cycle allowing to proposing mouse estrous cycle as a physiological model for studying VE-cadherin phosphorylation in vivo. The analysis of VE-cadherin Y685F knock-in mice (VE-Y685F) showed that these mice exhibit a higher vascular permeability in uterus and ovaries and the skin small capillaries compared to wild-type animals. Moreover, VE-Y685F mice presented higher levels of soluble VE-cadherin compared to wild-type counterparts in two induced arthritis model. Altogether, sVE and VE-cadherin phosphorylation present an array of interests for RA therapies as well as developing new therapeutic tools in RA and other vascular diseases.</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
</country>
<region><li>Auvergne-Rhône-Alpes</li>
<li>Rhône-Alpes</li>
</region>
<settlement><li>Grenoble</li>
</settlement>
<orgName><li>Université Grenoble-Alpes</li>
</orgName>
</list>
<tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Sidibe, Adama" sort="Sidibe, Adama" uniqKey="Sidibe A" first="Adama" last="Sidibe">Adama Sidibe</name>
</region>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Psychologie/explor/BernheimV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000142 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000142 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Psychologie |area= BernheimV1 |flux= Main |étape= Exploration |type= RBID |clé= Hal:tel-00819876 |texte= VE-cadherin post-translational modifications : from molecular mechanisms to clinical applications : from molecular mechanisms to clinical applications }}
This area was generated with Dilib version V0.6.33. |