Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration
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- Noura El-Jamal
- INSERM U995, Lille, France;
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- Edmone Erdual
- INSERM U995, Lille, France;
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- Michel Neunlist
- INSERM 913, CHU Hôtel Dieu, Nantes, France;
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- Dine Koriche
- CHU Lille, Service des maladies de l'appareil digestif et de la nutrition, Hôpital Claude Huriez, Lille, France;
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- Caroline Dubuquoy
- INSERM U995, Lille, France;
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- Francois Maggiotto
- INSERM U995, Lille, France;
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- Julien Chevalier
- INSERM 913, CHU Hôtel Dieu, Nantes, France;
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- Dominique Berrebi
- Université Paris-Sud, Laboratoire “Cytokines, Chimiokines et Immunopathologie,” Unité Mixte de Recherche S996, Clamart, France;
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- Laurent Dubuquoy
- INSERM U995, Lille, France;
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- Eric Boulanger
- Université Lille Nord de France, Lille, France;
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- Antoine Cortot
- INSERM U995, Lille, France;
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- Pierre Desreumaux
- INSERM U995, Lille, France;
抄録
<jats:p> 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. </jats:p>
収録刊行物
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- American Journal of Physiology-Gastrointestinal and Liver Physiology
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American Journal of Physiology-Gastrointestinal and Liver Physiology 307 (3), G274-G285, 2014-08-01
American Physiological Society