Autoren:	Pontarollo, Giulia Mann, Amrit Brandão, Inês Malinarich, Frano Schöpf, Marie Reinhardt, Christoph
Titel:	Protease-activated receptor signaling in intestinal permeability regulation
Online-Publikationsdatum:	15-Jun-2022
Erscheinungsdatum:	2020
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Protease-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.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7158
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	The FEBS journal 287 4
Seitenzahl oder Artikelnummer:	645 658
Verlag:	Wiley-Blackwell
Verlagsort:	Oxford u.a
Erscheinungsdatum:	2020
ISSN:	1742-4658
DOI der Originalveröffentlichung:	10.1111/febs.15055
Enthalten in den Sammlungen:	JGU-Publikationen