Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration

Autor: Michel Neunlist, Dine Koriche, Laurent Dubuquoy, Pierre Desreumaux, Dominique Berrebi, Julien Chevalier, Caroline Dubuquoy, Eric Boulanger, Edmone Erdual, Antoine Cortot, Noura El-Jamal, François Maggiotto
Rok vydání: 2014
Předmět:
Pathology
Time Factors
Physiology
Receptor expression
Anti-Inflammatory Agents
Enteroendocrine cell
Inflammatory bowel disease
Jurkat Cells
Mice
Glucagon-Like Peptide 2
Receptors
Glucagon
Mesenteric lymph nodes
digestive
oral
and skin physiology
Dextran Sulfate
Gastroenterology
Hep G2 Cells
Colitis
Liver regeneration
Recombinant Proteins
medicine.anatomical_structure
Liver
Glucagon-Like Peptide-2 Receptor
medicine.symptom
HT29 Cells
hormones
hormone substitutes
and hormone antagonists
endocrine system
medicine.medical_specialty
Colon
Enteroendocrine Cells
Inflammation
Biology
Gastrointestinal Agents
Physiology (medical)
medicine
Animals
Hepatectomy
Humans
RNA
Messenger
Hepatology
medicine.disease
Peptide Fragments
Liver Regeneration
Rats
Mice
Inbred C57BL
Disease Models
Animal
Gene Expression Regulation
Trinitrobenzenesulfonic Acid
Cancer research
Intestinal Disorder
Caco-2 Cells
Zdroj: American journal of physiology. Gastrointestinal and liver physiology. 307(3)
ISSN: 1522-1547
Popis: 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.
Databáze: OpenAIRE
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