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dc.contributor.authorSpenle, Carolineen_US
dc.contributor.authorLefebvre, Olivieren_US
dc.contributor.authorLacroute, Joelen_US
dc.contributor.authorMechine-Neuville, Agnesen_US
dc.contributor.authorBarreau, Fredericken_US
dc.contributor.authorBlottiere, Herve Men_US
dc.contributor.authorDuclos, Bernarden_US
dc.contributor.authorArnold, Christianeen_US
dc.contributor.authorHussenet, Thomasen_US
dc.contributor.authorHemmerle, Josephen_US
dc.contributor.authorGullberg, Donalden_US
dc.contributor.authorKedinger, Micheleen_US
dc.contributor.authorSorokin, Lydiaen_US
dc.contributor.authorOrend, Gertrauden_US
dc.contributor.authorSimon-Assmann, Patriciaen_US
dc.date.accessioned2015-03-30T09:02:52Z
dc.date.available2015-03-30T09:02:52Z
dc.date.issued2014-10-27eng
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/1956/9697
dc.description.abstractLaminins (LM), basement membrane molecules and mediators of epithelial-stromal communication, are crucial in tissue homeostasis. Inflammatory Bowel Diseases (IBD) are multifactorial pathologies where the microenvironment and in particular LM play an important yet poorly understood role in tissue maintenance, and in cancer progression which represents an inherent risk of IBD. Here we showed first that in human IBD colonic samples and in murine colitis the LMα1 and LMα5 chains are specifically and ectopically overexpressed with a concomitant nuclear p53 accumulation. Linked to this observation, we provided a mechanism showing that p53 induces LMα1 expression at the promoter level by ChIP analysis and this was confirmed by knockdown in cell transfection experiments. To mimic the human disease, we induced colitis and colitis-associated cancer by chemical treatment (DSS) combined or not with a carcinogen (AOM) in transgenic mice overexpressing LMα1 or LMα5 specifically in the intestine. We demonstrated that high LMα1 or LMα5 expression decreased susceptibility towards experimentally DSS-induced colon inflammation as assessed by histological scoring and decrease of pro-inflammatory cytokines. Yet in a pro-oncogenic context, we showed that LM would favor tumorigenesis as revealed by enhanced tumor lesion formation in both LM transgenic mice. Altogether, our results showed that nuclear p53 and associated overexpression of LMα1 and LMα5 protect tissue from inflammation. But in a mutation setting, the same LM molecules favor progression of IBD into colitis-associated cancer. Our transgenic mice represent attractive new models to acquire knowledge about the paradoxical effect of LM that mediate either tissue reparation or cancer according to the microenvironment. In the early phases of IBD, reinforcing basement membrane stability/organization could be a promising therapeutic approach.en_US
dc.language.isoengeng
dc.publisherPLoSeng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0eng
dc.titleThe laminin response in inflammatory bowel disease: Protection or malignancy?en_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2015-03-03T16:11:10Zen_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2014 2014 Spenlé et al
dc.source.articlenumbere111336
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0111336
dc.identifier.cristin1203750
dc.source.journalPLoS ONE
dc.source.409
dc.source.1410
dc.subject.nsiVDP::Medical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical biochemistry: 726eng
dc.subject.nsiVDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk biokjemi: 726nob


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