{"id":840,"date":"2017-05-15T10:55:23","date_gmt":"2017-05-15T08:55:23","guid":{"rendered":"http:\/\/lbti.ibcp.fr\/?page_id=840"},"modified":"2021-04-21T18:57:25","modified_gmt":"2021-04-21T16:57:25","slug":"xxxxxxxx-2","status":"publish","type":"page","link":"https:\/\/lbti.ibcp.fr\/?page_id=840","title":{"rendered":"R\u00f4le des m\u00e9talloprot\u00e9ases et de leurs prot\u00e9ines r\u00e9gulatrices dans la cicatrisation"},"content":{"rendered":"

Porteur de projet<\/strong><\/em>\u00a0:<\/span> C. Moali<\/a><\/strong><\/p>\n

\n

La cicatrisation est un exemple de processus impliquant un remodelage important, avec plusieurs \u00e9tapes : h\u00e9mostase, inflammation, angiogen\u00e8se, r\u00e9-\u00e9pith\u00e9lialisation, formation d\u2019une matrice extracellulaire provisoire (tissu de granulation), contraction de la plaie et remodelage matriciel. Les prot\u00e9ases BMP-1\/tolloid-like (BTPs) jouant un r\u00f4le essentiel dans l\u2019assemblage de la matrice, nous avons suppos\u00e9 qu\u2019elles seraient surexprim\u00e9es au moment des phases de granulation et de remodelage. Ceci a \u00e9t\u00e9 d\u00e9montr\u00e9 dans un mod\u00e8le de cicatrisation de la corn\u00e9e ainsi que sur des corn\u00e9es humaines issues de patients ayant subi une transplantation (figure). Nous caract\u00e9risons \u00e9galement d\u2019autres types de processus de r\u00e9paration tissulaire (peau et c\u0153ur) pour d\u00e9terminer si cette observation est g\u00e9n\u00e9ralisable.<\/span><\/p>\n

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D\u00e9tection par immuno-fluorescence des prot\u00e9ases BMP-1\/mTLD et de la prot\u00e9ine r\u00e9gulatrice PCPE-1 au niveau d\u2019une l\u00e9sion centrale de la corn\u00e9e ayant conduit \u00e0 la formation d\u2019une opacit\u00e9 corn\u00e9enne (D\u2019apr\u00e8s Malecaze et al. Invest. Ophthalmol. Vis. Sci. 2014).<\/span><\/em><\/h5>\n

Pour mieux comprendre le r\u00f4le jou\u00e9 par les BTPs et les prot\u00e9ases associ\u00e9es (ADAMTS-2, 3 et 14 ; m\u00e9prines \u03b1 et \u03b2) dans la cicatrisation, nous utilisons des approches de prot\u00e9omique quantitative qui permettent de mettre en \u00e9vidence les substrats cliv\u00e9s par ces prot\u00e9ases dans des mod\u00e8les cellulaires ou tissulaires. Ces approches nous ont permis de r\u00e9v\u00e9ler plusieurs nouvelles fonctions des BTPs et des ADAMTSs, notamment dans le contr\u00f4le de l’adh\u00e9sion cellulaire et de l\u2019activit\u00e9 du TGF-\u03b2 qui r\u00e9gule plusieurs aspects fondamentaux de la cicatrisation (inflammation, synth\u00e8se des prot\u00e9ines matricielles, contraction des plaies).<\/span><\/p>\n

Principales techniques utilis\u00e9es<\/u><\/span><\/p>\n

\u2022 PCR quantitative<\/span><\/p>\n

\u2022 Immuno-fluorescence \/ western-blots \/ ELISA<\/span><\/p>\n

\u2022 Biologie cellulaire<\/span><\/p>\n

\u2022 Tests enzymatiques<\/span><\/p>\n

\u2022 Spectrom\u00e9trie de masse et analyse prot\u00e9omique
\n<\/u><\/span><\/p>\n

\n

S\u00e9lection de publications :<\/strong><\/em><\/span><\/p>\n

BMP-1 disrupts cell adhesion and enhances TGF-beta activation through cleavage of the matricellular protein thrombospondin-1. <\/span>Anastasi C,\u00a0 Rousselle P, Talantikite M, Tessier T, Cluzel C, Bachmann A, Mariano N, Dussoyer M, Alcaraz LB, Fortin L, Aubert A, Delolme F, El Kholti N, Armengaud J, Fourni\u00e9 P, Auxenfans C, Valcourt U, Vadon-Le Goff S, Moali C. Science Signaling <\/cite><\/em>2020; 13(639): eaba3880.<\/p>\n

C-terminal proteolysis of the collagen VI \u03b13 chain by BMP-1 and proprotein convertase(s) releases endotrophin in fragments of different sizes.<\/a> Heum\u00fcller SE, Talantikite M, Napoli M, Armengaud J, M\u00f6rgelin M, Hartmann U, Sengle G, Paulsson M, Moali C, Wagener R. J Biol Chem<\/span>.<\/em> 2019;294(37):13769-13780.<\/p>\n

Interaction of Complement Defence Collagens C1q and Mannose-Binding Lectin with BMP-1\/Tolloid-like Proteinases.<\/a> Lacroix M, Tessier A, Dumestre-P\u00e9rard C, Vadon-Le Goff S, Gout E, Bruckner-Tuderman L, Kiritsi D, Nystr\u00f6m A, Ricard-Blum S, Moali C, Hulmes DJS, Thielens NM. Sci Rep<\/span>.<\/em> 2017;7(1):16958.<\/p>\n

Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-\u03b2 signaling as primary targets.<\/a> Bekhouche M, Leduc C, Dupont L, Janssen L, Delolme F, Vadon-Le Goff S, Smargiasso N, Baiwir D, Mazzucchelli G, Zanella-Cleon I, Dubail J, De Pauw E, Nusgens B, Hulmes DJ, Moali C, Colige A. FASEB J.<\/em> 2016;30(5):1741-56.<\/p>\n

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Proteolytic control of TGF-\u03b2 co-receptor activity by BMP-1\/tolloid-like proteases revealed by quantitative iTRAQ proteomics.<\/a> Delolme F, Anastasi C, Alcaraz LB, Mendoza V, Vadon-Le Goff S, Talantikite M, Capomaccio R, Mevaere J, Fortin L, Mazzocut D, Damour O, Zanella-Cl\u00e9on I, Hulmes DJ, Overall CM, Valcourt U, Lopez-Casillas F, Moali C. Cell Mol Life Sci.<\/em> 2015;72(5):1009-27.<\/span><\/p>\n

Upregulation of bone morphogenetic protein-1\/mammalian tolloid and procollagen C-proteinase enhancer-1 in corneal scarring.<\/a> Malecaze F, Massoudi D, Fourni\u00e9 P, Tricoire C, Cassagne M, Malbouyres M, Hulmes DJ, Moali C, Galiacy SD. Invest Ophthalmol Vis Sci.<\/em> 2014;55(10):6712-21<\/p>\n

\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Porteur de projet\u00a0: C. Moali La cicatrisation est un exemple de processus impliquant un remodelage important, avec plusieurs \u00e9tapes : h\u00e9mostase, inflammation, angiogen\u00e8se, r\u00e9-\u00e9pith\u00e9lialisation, formation d\u2019une matrice extracellulaire provisoire (tissu de granulation), contraction de la plaie et remodelage matriciel. Les prot\u00e9ases BMP-1\/tolloid-like (BTPs) jouant un r\u00f4le essentiel dans l\u2019assemblage de la matrice, nous avons suppos\u00e9<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":105,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-840","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/pages\/840","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=840"}],"version-history":[{"count":20,"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/pages\/840\/revisions"}],"predecessor-version":[{"id":4591,"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/pages\/840\/revisions\/4591"}],"up":[{"embeddable":true,"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/pages\/105"}],"wp:attachment":[{"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=840"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}