112758 20230519145617.0 doi 10.1016/j.biopha.2021.112239 sideral 127533 ART-2021-127533 eng Guijarro, Luis G. Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved 2021 Access copy available to the general public Unrestricted 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 ß-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. © 2021 The Authors info:eu-repo/grantAgreement/ES/ISCIII/FIS/12-02557 info:eu-repo/grantAgreement/ES/ISCIII/PI13-00041 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 7.419 2021 PHARMACOLOGY & PHARMACY 26 / 279 = 0.093 2021 Q1 T1 MEDICINE, RESEARCH & EXPERIMENTAL 30 / 140 = 0.214 2021 Q1 T1 1.194 2021 Pharmacology 2021 Q1 Medicine (miscellaneous) 2021 Q1 11.6 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Cano-Martínez, David Toledo-Lobo, M.Val Salinas, Patricia Sanmartín Chaparro, María Gómez-Lahoz, Ana M. Zoullas, Sofía Rodríguez-Torres, Rosa Román, Irene D. Monasor, Laura Sebastián Ruiz-Llorente, Lidia del Carmen Boyano-Adánez, María Guerra, Iván Iborra, Marisa Cabriada, José Luis Bujanda, Luis Taxonera, Carlos García-Sánchez, Valle Marín-Jiménez, Ignacio Acosta, Manuel Barreiro-de Vera, Isabel Martín-Arranz, María Dolores Mesonero, Francisco Sempere, Laura Gomollón, Fernando Universidad de Zaragoza (orcid)0000-0003-0076-3529 Hinojosa, Joaquín Alvarez-Mon, Melchor Gisbert, Javier P. Ortega, Miguel A. Hernández-Breijo, Borja 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 144 (2021), 112239 [12 pp.] Biomed. pharmacother. BIOMEDICINE & PHARMACOTHERAPY 0753-3322 5412219 http://zaguan.unizar.es/record/112758/files/texto_completo.pdf Versión publicada 2491460 http://zaguan.unizar.es/record/112758/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:112758 articulos driver 2023-05-18-16:12:06 ARTICLE