title: Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration.
abstract: The glucagon-like peptide 2 (GLP-2) is an intestinotrophic hormone with growth promoting and anti-inflammatory actions. However, the full biological functions of GLP-2 and the localization of its receptor (GLP-2R) remain controversial. Among cell lines tested, the expression of GLP-2R transcript was detected in human colonic myofibroblasts (CCD-18Co) and in primary culture of rat enteric nervous system but not in intestinal epithelial cell lines, lymphocytes, monocytes, or endothelial cells. Surprisingly, GLP-2R was expressed in murine (GLUTag), but not human (NCI-H716) enteroendocrine cells. The screening of GLP-2R mRNA in mice organs revealed an increasing gradient of GLP-2R toward the distal gut. An unexpected expression was detected in the mesenteric fat, mesenteric lymph nodes, bladder, spleen, and liver, particularly in hepatocytes. In two mice models of trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis, the colonic expression of GLP-2R mRNA was decreased by 60% compared with control mice. Also, GLP-2R mRNA was significantly downregulated in intestinal tissues of inflammatory bowel disease patients. Therapeutically, GLP-2 showed a weak restorative effect on intestinal inflammation during TNBS-induced colitis as assessed by macroscopic score and inflammatory markers. Finally, GLP-2 treatment accelerated mouse liver regeneration following partial hepatectomy as assessed by histological and molecular analyses. In conclusion, the limited therapeutic effect of GLP-2 on colonic inflammation dampens its utility in the management of severe inflammatory intestinal disorders. However, the role of GLP-2 in liver regeneration is a novelty that might introduce GLP-2 into the management of liver diseases and emphasizes on the importance of elucidating other extraintestinal functions of GLP-2.
authors.affiliation: INSERM U995, Lille, France; Université Lille Nord de France, Lille, France; Intestinal Biotech Development, Lille, France;
authors.forename: Noura
authors.initials: N
authors.lastname: El-Jamal
authors.affiliation: INSERM U995, Lille, France; Université Lille Nord de France, Lille, France;
authors.forename: Edmone
authors.initials: E
authors.lastname: Erdual
authors.affiliation: INSERM 913, CHU Hôtel Dieu, Nantes, France;
authors.forename: Michel
authors.initials: M
authors.lastname: Neunlist
authors.affiliation: CHU Lille, Service des maladies de l'appareil digestif et de la nutrition, Hôpital Claude Huriez, Lille, France;
authors.forename: Dine
authors.initials: D
authors.lastname: Koriche
authors.affiliation: INSERM U995, Lille, France; Intestinal Biotech Development, Lille, France;
authors.forename: Caroline
authors.initials: C
authors.lastname: Dubuquoy
authors.affiliation: INSERM U995, Lille, France; Université Lille Nord de France, Lille, France;
authors.forename: Francois
authors.initials: F
authors.lastname: Maggiotto
authors.affiliation: INSERM 913, CHU Hôtel Dieu, Nantes, France;
authors.forename: Julien
authors.initials: J
authors.lastname: Chevalier
authors.affiliation: Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie," Unité Mixte de Recherche S996, Clamart, France; INSERM, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Clamart, France; Service d'Anatomie et de Cytologie Pathologique, Unité Propre de Recherche de l'Enseignement Supérieur Associé 1320, Hôpital Robert Debré, France; Université Denis Diderot, Université Paris 7, Paris, France; and.
authors.forename: Dominique
authors.initials: D
authors.lastname: Berrebi
authors.affiliation: INSERM U995, Lille, France; Université Lille Nord de France, Lille, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Dubuquoy
authors.affiliation: Université Lille Nord de France, Lille, France; EA 2693, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Boulanger
authors.affiliation: INSERM U995, Lille, France; Université Lille Nord de France, Lille, France; CHU Lille, Service des maladies de l'appareil digestif et de la nutrition, Hôpital Claude Huriez, Lille, France;
authors.forename: Antoine
authors.initials: A
authors.lastname: Cortot
authors.affiliation: INSERM U995, Lille, France; Université Lille Nord de France, Lille, France; CHU Lille, Service des maladies de l'appareil digestif et de la nutrition, Hôpital Claude Huriez, Lille, France; pdesreumaux@hotmail.com.
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005786:Gene Expression Regulation; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D000067758:Glucagon-Like Peptide-2 Receptor; D019073:HT29 Cells; D056945:Hep G2 Cells; D006498:Hepatectomy; D006801:Humans; D019169:Jurkat Cells; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D053767:Glucagon-Like Peptide 2; D000067758:Glucagon-Like Peptide-2 Receptor; D010446:Peptide Fragments; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D011994:Recombinant Proteins; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate
keywords: enteroendocrine cell; glucagon-like peptide; inflammatory bowel disease