RT Journal Article
T1 Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved.
A1 Guijarro, Luis G
A1 Cano-Martínez, David
A1 Toledo-Lobo, M Val
A1 Salinas, Patricia Sanmartín
A1 Chaparro, María
A1 Gómez-Lahoz, Ana M
A1 Zoullas, Sofía
A1 Rodríguez-Torres, Rosa
A1 Román, Irene D
A1 Monasor, Laura Sebastián
A1 Ruiz-Llorente, Lidia
A1 Del Carmen Boyano-Adánez, María
A1 Guerra, Iván
A1 Iborra, Marisa
A1 Cabriada, José Luis
A1 Bujanda, Luis
A1 Taxonera, Carlos
A1 García-Sánchez, Valle
A1 Marín-Jiménez, Ignacio
A1 Acosta, Manuel Barreiro-de
A1 Vera, Isabel
A1 Martín-Arranz, María Dolores
A1 Mesonero, Francisco
A1 Sempere, Laura
A1 Gomollón, Fernando
A1 Hinojosa, Joaquín
A1 Alvarez-Mon, Melchor
A1 Gisbert, Javier P
A1 Ortega, Miguel A
A1 Hernández-Breijo, Borja
A1 On Behalf Of The Predicrohn Study Group From Geteccu, 
K1 Adalimumab
K1 IGF-1
K1 Inflammatory bowel diseases
AB 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.
YR 2021
FD 2021-09-30
LK https://hdl.handle.net/10668/25733
UL https://hdl.handle.net/10668/25733
LA en
DS RISalud
RD Apr 8, 2025