{ "items" : [ { "id" : "http://www.idref.fr/215220609/id" "properties" : { "http://www.w3.org/1999/02/22-rdf-syntax-ns#type" : [ "http://rdaregistry.info/Elements/c/C10001", "http://purl.org/vocab/frbr/core#Work" ] , "http://id.loc.gov/vocabulary/relators/ths" : [ "http://www.idref.fr/147705126/id", "http://www.idref.fr/074574221/id" ] , "http://id.loc.gov/vocabulary/relators/aut" : [ "http://www.idref.fr/167587013/id" ] , "http://www.w3.org/2004/02/skos/core#altLabel" : [ "Intestinal and skin homeostasis, targeting inflammation and cancer" ] , "http://purl.org/dc/elements/1.1/subject" : [ "Peau", "Canc\u00E9rogen\u00E8se", "Maladies inflammatoires intestinales", "Tumeurs colorectales -- Dissertation universitaire", "R\u00E9cepteurs activ\u00E9s par les prolif\u00E9rateurs de peroxysomes -- Dissertation universitaire", "Th\u00E9rapeutique exp\u00E9rimentale", "Inflammation", "Mod\u00E8les animaux", "Mod\u00E8les animaux -- Dissertation universitaire", "Tumeurs colorectales", "R\u00E9cepteurs activ\u00E9s par les prolif\u00E9rateurs de peroxysomes", "Ent\u00E9roglucagon", "Intestins -- Maladies", "Syndrome de Lynch", "R\u00E9cepteurs PPAR", "Th\u00E8ses et \u00E9crits acad\u00E9miques", "MICI", "Glucagon-like peptide 2 -- Dissertation universitaire", "Hom\u00E9ostasie -- Dissertation universitaire", "Glucagon-like peptide 2", "Maladies inflammatoires intestinales -- Dissertation universitaire", "Hom\u00E9ostasie", "Peau -- Dissertation universitaire" ] , "http://www.w3.org/2004/02/skos/core#prefLabel" : [ "Hom\u00E9ostasie de l'intestin et de la peau, cibles et mod\u00E8les pour \u00E9tudier l'inflammation et la carcinogen\u00E8se" ] , "http://purl.org/dc/terms/language" : [ "http://lexvo.org/id/iso639-3/eng" ] , "http://purl.org/dc/terms/subject" : [ "http://www.idref.fr/114595666/id", "http://www.idref.fr/148223591/id", "http://www.idref.fr/027659607/id", "http://www.idref.fr/040780074/id", "http://www.idref.fr/027289729/id", "http://www.idref.fr/04071991X/id", "http://www.idref.fr/040802515/id", "http://www.idref.fr/110678508/id", "http://www.idref.fr/11461234X/id", "http://www.idref.fr/040802795/id", "http://www.idref.fr/027340988/id", "http://www.idref.fr/027253139/id", "http://www.idref.fr/040839486/id", "http://www.idref.fr/027834417/id", "http://www.idref.fr/035173718/id", "http://www.idref.fr/05930992X/id", "http://www.idref.fr/027742520/id", "http://www.idref.fr/027836754/id" ] , "http://purl.org/dc/elements/1.1/title" : [ "Hom\u00E9ostasie de l'intestin et de la peau, cibles et mod\u00E8les pour \u00E9tudier l'inflammation et la carcinogen\u00E8se" ] , "http://id.loc.gov/vocabulary/relators/dgg" : [ "http://www.idref.fr/026404389/id" ] , "http://www.w3.org/2004/02/skos/core#note" : [ "L\u2019hom\u00E9ostasie des muqueuses intestinale et cutan\u00E9e d\u00E9pend des interactions complexes entre le microbiote, l\u2019\u00E9pith\u00E9lium et le syst\u00E8me immunitaire de l\u2019h\u00F4te. Des m\u00E9canismes r\u00E9gulateurs divers coop\u00E8rent afin de maintenir l\u2019\u00E9quilibre physiologique, et un d\u00E9faut dans ces m\u00E9canismes entrainent des situations pathologiques. Le glucagon like peptide 2 (GLP-2) est un neuropeptide caract\u00E9ris\u00E9 par des propri\u00E9t\u00E9s prolif\u00E9ratives et anti-inflammatoires. Le potentiel th\u00E9rapeutique des analogues de GLP-2 est actuellement \u00E9valu\u00E9 dans des essais cliniques pour des maladies digestives. Les effets du GLP-2 dans l\u2019intestin sont m\u00E9di\u00E9s par son r\u00E9cepteur GLP-2 receptor (GLP-2R). Malgr\u00E9 la pr\u00E9sence des nombreuses \u00E9tudes \u00E9valuant l\u2019expression cellulaire et la distribution tissulaire du GLP-2R, celles-ci restent controvers\u00E9es, que ca soit chez l\u2019homme ou les rongeurs. Il est admis que l\u2019expression du GLP-2R \u00E9tait confin\u00E9e au tube digestif, principalement \u00E0 l\u2019intestin proximal, malgr\u00E9 des \u00E9tudes \u00E9voquant une expression extra-intestinale. Une meilleure compr\u00E9hension de l\u2019expression et de la distribution de GLP-2R est n\u00E9cessaire pour \u00E9lucider les fonctions biologiques de GLP-2. Nous avons r\u00E9alis\u00E9 une cartographie de l\u2019expression de GLP-2R dans diff\u00E9rents organes murins ainsi que dans des lign\u00E9es immortalis\u00E9es humaines et murines. Nous avons \u00E9galement \u00E9valu\u00E9 l\u2019expression intestinale du GLP-2R dans 2 mod\u00E8les de colites induites chez la souris et dans des biopsies intestinales des patients atteints de maladies inflammatoires chroniques de l\u2019intestin (MICI). Nous avons d\u00E9montr\u00E9 que GLP-2R \u00E9tait exprim\u00E9 en dehors du tube digestif notamment dans la vessie, le syst\u00E8me nerveux central, le m\u00E9sent\u00E8re, les ganglions m\u00E9sent\u00E9riques, la rate et le foie. Nous avons \u00E9galement montr\u00E9 que la plus forte expression de GLP-2R dans le tube digestif \u00E9tait d\u00E9tect\u00E9e dans le colon proximal et le rectum. Dans les mod\u00E8les murins de colites et chez les patients atteints de MICI, l\u2019expression du GLP-2R \u00E9tait diminu\u00E9e, notamment dans les zones inflammatoires. Ceci pose la question le r\u00F4le physiopathologique des analogues de GLP-2 dans les maladies inflammatoires digestives. En conclusion, les hypoth\u00E8ses pr\u00E9c\u00E9dentes consid\u00E9rant une expression du GLP-2R majoritaire dans le tube proximal doivent \u00EAtre reconsid\u00E9r\u00E9es. Les fonctions physiologiques extra-intestinales du GLP-2 doivent \u00EAtre explor\u00E9s afin d\u2019anticiper des effets ind\u00E9sirables extra-digestifs des analogues de GLP2.", "Intestinal and skin physiologies are quite similar as far as the homeostasis in both depends on complex interactions between the microbiota, the epithelium and the host immune system. Diverse regulatory mechanisms cooperate to maintain the equilibrium, and a breakdown in these pathways may precipitate pathological conditions. Glucagon like peptide 2 (GLP-2) represents one of the hot topics in research in intestinal physiology. Its dual function as an anti-inflammatory agent and growth factor has led to its consideration in therapeutic strategies and GLP-2 analogs are currently in clinical trials for several digestive diseases. The integrative responses to GLP-2 are mediated via the GLP-2 receptor (GLP-2R). Despite extensive research, precise tissue distribution of GLP-2R expression remains controversial both in rodents and humans. It is widely believed that GLP-2R expression is restricted to the gastrointestinal tract, mainly to the proximal bowel, despite the presence of few studies reporting extra-intestinal expression. Thus, to enhance our knowledge concerning the potential functions of GLP-2 analogs, a better understanding for GLP-2R expression is considered necessary. We therefore realized a panel of GLP-2R expression in mice tissues and in several human, murine and rat cells lines. Given the therapeutic beneficial effects of GLP-2 analogs in intestinal disorders, we investigated the intestinal expression of GLP-2R in mice models of chemically-induced colitis and in inflammatory bowel disease (IBD) patients. We demonstrated that GLP-2R is more widely expressed than expected with significant expression in several mice tissues including bladder, central nervous system, mesenteric adipose tissue, mesenteric lymph nodes, spleen, and liver. We also showed that the expression of GLP-2R in the gastrointestinal tract follows an increasing gradient toward the distal gut with highest expression in the colon and rectum. Interestingly, the intestinal expression of GLP-2R is significantly decreased in experimental mice models of colitis and in IBD patients which raised the point of the physiological role of GLP-2 analogs in digestive disease patients. Overall, previous hypotheses limiting GLP-2R expression and function to proximal bowel need to be revisited, and further studies should address the extra-intestinal biological function of GLP-2." ] , "http://purl.org/dc/elements/1.1/type" : [ "Text" ] , "http://iflastandards.info/ns/isbd/elements/P1001" : [ "http://iflastandards.info/ns/isbd/terms/contentform/T1009" ] , "http://rdaregistry.info/Elements/w/P10219" : [ "2012" ] , "http://rdaregistry.info/Elements/u/P60049" : [ "http://rdaregistry.info/termList/RDAContentType/1020"] } } }