Mostrar el registro sencillo del ítem

dc.contributor.authorQuilichini, Evans
dc.contributor.authorFabre, Mélanie
dc.contributor.authorDirami, Thassadite
dc.contributor.authorStedman, Aline
dc.contributor.authorDe Vas, Matias
dc.contributor.authorOzguc, Ozge
dc.contributor.authorPasek, Raymond C
dc.contributor.authorCereghini, Silvia
dc.contributor.authorMorillon, Lucie
dc.contributor.authorGuerra, Carmen 
dc.contributor.authorCouvelard, Anne
dc.contributor.authorGannon, Maureen
dc.contributor.authorHaumaitre, Cécile
dc.date.accessioned2019-07-02T08:46:25Z
dc.date.available2019-07-02T08:46:25Z
dc.date.issued2019-06-20
dc.identifier.citationCell Mol Gastroenterol Hepatol. 2019 . pii: S2352-345X(19)30084-0es_ES
dc.identifier.issn2352345Xes_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7837
dc.description.abstractBACKGROUND AND AIMS: The exocrine pancreas consists of acinar cells that produce digestive enzymes transported to the intestine through a branched ductal epithelium. Chronic pancreatitis is characterized by progressive inflammation, fibrosis and loss of acinar tissue. These changes of the exocrine tissue are risk factors for pancreatic cancer. The cause of chronic pancreatitis cannot be identified in one-quarter of patients. Here, we investigated how duct dysfunction could contribute to pancreatitis development. METHODS: The transcription factor Hnf1b, first expressed in pancreatic progenitors, is strictly restricted to ductal cells from late embryogenesis. We have previously shown that Hnf1b is crucial for pancreas morphogenesis but its postnatal role still remains unelucidated. To investigate the role of pancreatic ducts in exocrine homeostasis, we inactivated Hnf1b gene in vivo in mouse ductal cells. RESULTS: We uncovered that postnatal Hnf1b inactivation in pancreatic ducts leads to chronic pancreatitis in adults. Hnf1bΔduct mutants display dilatation of ducts, loss of acinar cells, acinar-to-ductal metaplasia (ADM) and lipomatosis. We deciphered the early events involved, with downregulation of cystic disease-associated genes, loss of primary cilia, upregulation of signaling pathways, especially Yap pathway involved in ADM. Remarkably, Hnf1bΔduct mutants developed pancreatic intraepithelial neoplasia and promote PanIN progression in concert with KRAS. We further showed that adult Hnf1b inactivation in pancreatic ducts is associated with impaired regeneration after injury, with persistent metaplasia and initiation of neoplasia. CONCLUSION: Loss of Hnf1b in ductal cells leads to chronic pancreatitis and neoplasia. This reveals that Hnf1b deficiency may contribute to diseases of the exocrine pancreas and could gain further insight into the etiology of pancreatitis and tumorigenesis.es_ES
dc.description.sponsorshipSupport to CH was received from theCentre National de la Recherche Scientifique (CNRS), the Universite Pierre et Marie Curie (UPMC)- Sorbonne Université , the GEFLUC - Les entreprises contre le Cancer, the Societe Francophone du Diabete (SFD)-Ypsomed, the programme Emergence UPMC. EQ was supported by a PhD fellowship from the French Ministère de la Recherche et de la Technologie. MF is an assistant engineer of the CNRS. TD and AS were supported by Sorbonne Université. MDV was supported by a PhD student fellowship from the European Marie Curie Initial Training Network (ITN)-Biology of Liver and Pancreatic Development and Disease (BOLD). O. O. was supported by a Master1 fellowship. RCP was supported by a postdoctoral fellowship from the American Heart Association (14POST20380262). MG was supported by the National Institutes of Health (U01 DK089540) and the Juvenile Diabetes Research Foundation (1-2011-592). CH is a permanent senior researcher of the Institut National de la Sante et de la Recherche Medicale (INSERM).es_ES
dc.language.isoenges_ES
dc.type.hasVersionAMes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectAcinar-to-ductal-metaplasiaes_ES
dc.subjectDuctses_ES
dc.subjectHnf1bes_ES
dc.subjectPancreatic canceres_ES
dc.subjectPancreatitises_ES
dc.titlePancreatic ductal deletion of Hnf1b disrupts exocrine homeostasis, leads to pancreatitis and facilitates tumorigenesises_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID31229598es_ES
dc.identifier.doi10.1016/j.jcmgh.2019.06.005es_ES
dc.contributor.funderFrench National Centre for Scientific Research (Francia) 
dc.contributor.funderSorbonne University (Francia) 
dc.contributor.funderSociété Francophone du Diabète 
dc.contributor.funderAmerican Heart Association 
dc.contributor.funderJuvenile Diabetes Research Foundation 
dc.contributor.funderInstitut National de la Santé et de la Recherche Médicale (Francia) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2352-345Xes_ES
dc.relation.publisherversionhttps://doi.org/ 10.1016/j.jcmgh.2019.06.005.es_ES
dc.identifier.journalCellular and molecular gastroenterology and hepatologyes_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Oncología Experimentales_ES
dc.rights.accessRightsopen accesses_ES


Ficheros en el ítem

Acceso Abierto
Thumbnail

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Atribución-NoComercial-CompartirIgual 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución-NoComercial-CompartirIgual 4.0 Internacional