Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved
EntityUAM. Departamento de Medicina
PublisherElsevier Masson s.r.l.
10.1016/j.biopha.2021.112239Biomedicine & Pharmacotherapy 144 (2021): 112239
Funded byThis research has been funded by grants from: Asociación Española de Gastroenterología (AEG), Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU), Instituto de Salud Carlos III (FIS12/02557 and PI13/00041) and Universidad de Alcalá (32/2013, 22/2014, 26/2015) and B2017/BMD-3804 MITIC-CM (Comunidad de Madrid) and Halekulani S.L.
ProjectGobierno de España. FIS12/02557; Gobierno de España. PI13/ 00041; Comunidad de Madrid. B2017/BMD-3804 MITIC-CM
SubjectsAdalimumab; IGF-1; Inflammatory bowel diseases; Medicina
Note"Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM"
Rights© 2021 The Authors
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of E-cadherin and β-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology.
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Google Scholar:Guijarro, Luis G. - Chaparro Sánchez, María - Vera, Isabel - Martín Arranz, María Dolores - Gisbert, Javier P. - PREDICROHN study group from GETECCU
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