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Protease‐activated receptor signaling in intestinal permeability regulation

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dc.contributor.authorPontarollo, Giulia
dc.contributor.authorMann, Amrit
dc.contributor.authorBrandão, Inês
dc.contributor.authorMalinarich, Frano
dc.contributor.authorSchöpf, Marie
dc.contributor.authorReinhardt, Christoph
dc.date.accessioned2019-12-11T15:46:34Z
dc.date.available2019-12-11T15:46:34Z
dc.date.issued2019
dc.description.abstractProtease-activated receptors (PARs) are a unique class of G-protein-coupled transmembrane receptors, which revolutionized the perception of proteases from degradative enzymes to context-specific signaling factors. Although PARs are traditionally known to affect several vascular responses, recent investigations have started to pinpoint the functional role of PAR signaling in the gastrointestinal (GI) tract. This organ is exposed to the highest number of proteases, either from the gut lumen or from the mucosa. Luminal proteases include the host's digestive enzymes and the proteases released by the commensal microbiota, while mucosal proteases entail extravascular clotting factors and the enzymes released from resident and infiltrating immune cells. Active proteases and, in case of a disrupted gut barrier, even entire microorganisms are capable to translocate the intestinal epithelium, particularly under inflammatory conditions. Especially PAR-1 and PAR-2, expressed throughout the GI tract, impact gut permeability regulation, a major factor affecting intestinal physiology and metabolic inflammation. In addition, PARs are critically involved in the onset of inflammatory bowel diseases, irritable bowel syndrome, and tumor progression. Due to the number of proteases involved and the multiple cell types affected, selective regulation of intestinal PARs represents an interesting therapeutic strategy. The analysis of tissue/cell-specific knockout animal models will be of crucial importance to unravel the intrinsic complexity of this signaling network. Here, we provide an overview on the implication of PARs in intestinal permeability regulation under physiologic and disease conditions.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1111/febs.15055pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.11/6814
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectCoagulationpt_PT
dc.subjectEpithelial barrier functionpt_PT
dc.subjectEpitheliumpt_PT
dc.subjectGastrointestinal cancerpt_PT
dc.subjectInflammatory bowel diseasept_PT
dc.subjectIntestinept_PT
dc.subjectMicrobial proteasespt_PT
dc.subjectMicrobiotapt_PT
dc.subjectProtease-activated receptorpt_PT
dc.subjectTissue factorpt_PT
dc.titleProtease‐activated receptor signaling in intestinal permeability regulationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleThe FEBS Journalpt_PT
person.familyNameSimões Brandão
person.givenNameMaria Inês
person.identifier.ciencia-idD913-F47A-931B
person.identifier.orcid0000-0003-3767-9515
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication96b963b3-a714-47b8-b14e-cf55294e9532
relation.isAuthorOfPublication.latestForDiscovery96b963b3-a714-47b8-b14e-cf55294e9532

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