Reference : Epithelial Rab guanine nucleotide exchange factor 1 (Rabgef1) deficiency increases su...
Scientific congresses and symposiums : Paper published in a book
Life sciences : Veterinary medicine & animal health
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/216439
Epithelial Rab guanine nucleotide exchange factor 1 (Rabgef1) deficiency increases susceptibility to DSS-induced intestinal inflammation in mice
English
El Abbas, Sophie mailto [Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Physiologie >]
Beguin, C [Université de Liège - ULiège > Laboratory of Cellular and Molecular Immunology, GIGA-Research and Faculty of Veterinary Medicine > > >]
Mesnil, Claire mailto [Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire >]
Schyns, Joey mailto [Université de Liège - ULiège > > > Doct. sc. vété. (paysage)]
Tsai, M [Stanford University School of Medicine, Stanford, California 94305-5324, USA > Department of Pathology > > >]
Tam, SY [Stanford University School of Medicine, Stanford, California 94305-5324, USA > Department of Pathology > > >]
Galli, SJ [Stanford University School of Medicine, Stanford, California 94305-5324, USA > Department of Pathology > > >]
Pirottin, Dimitri mailto [Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Département des sciences fonctionnelles (DSF) >]
Bureau, Fabrice mailto [Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire >]
Marichal, Thomas mailto [Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire >]
21-Oct-2016
Proceedings: 3rd FARAH-DAY
No
No
National
Liège
Belgique
3rd FARAH-Day, Faculté de Médecine Vétérinaire, ULiège
21 novembre 2016
Liège
Belgique
[en] Rab guanine nucleotide exchange factor (GEF)1 (Rabgef1) is a guanine nucleotide exchange factor for the endocytic GTPase Rab5, and also exhibits E3 ubiquitin ligase activity in vitro. In vivo functions of Rabgef1 remain largely unknown, but Rabgef1 is critical for health, as globally Rabgef1-deficient mice exhibit perinatal mortality and those surviving to adulthood spontaneously develop severe skin inflammation.This protein is highly expressed in murine intestinal epithelial cells (IECs).
Objective: The aim of this study is to clarify the role of Rabgef1 in murine IECs
Materials and methods: We performed conditional deletion of Rabgef1 using the cre-lox system to obtain mice lacking Rabgef1 specifically in IECs (Rabgef1IEC-KO).
Results: Rabgef1IEC-KO mice did not develop spontaneous intestinal abnormalities but showed an increased susceptibility to inflammation in dextran sodium sulfate (DSS)-induced col itis model. Indeed, compared to littermate controls, mice lacking Rabgef1 in IECs exhibited shorter and highly inflamed colons and higher inflammatory scores in histopathological examination of colons, suggesting that Rabgef1 expression regulates IEC function and is critical in limiting DSS induced inflammation and damage. In addition, we also showed that mRNA expression of pro-inflammatory cytokines, such as Il1b and Tnfa, was upregulated in IECs isolated from Rabgef1IEC-KO mice compared to the ones isolated from littermate controls.
Conclusion: Taken together, these results suggest that Rabgef1 acts as a regulator of intestinal homeostasis, and that dysregulated Rabgef1 expression could contribute to intestinal barrier dysfunction in inflammatory conditions of the gut.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/216439

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