Portal de investigación
Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Guijarro, Luis G.
- Cano-Martinez, David
- Toledo-Lobo, M. Val
- Salinas PS
- Chaparro, Maria
- Gomez-Lahoz, Ana M.
- Zoullas, Sofia
- Rodriguez-Torres, Rosa
- Roman, Irene D.
- Monasor LS
- Ruiz-Llorente, Lidia
- del Carmen Boyano-Adanez, Maria
- Guerra, Ivan
- Cabriada JL
- Bujanda, Luis
- Taxonera, Carlos
- Garcia-Sanchez, Valle
- Marin-Jimenez, Ignacio
- Acosta MB
- Vera, Isabel
- Martín-Arranz MD
- Mesonero, Francisco
- Sempere, Laura
- Gomollon, Fernando
- Hinojosa, Joaquin
- Alvarez-Mon, Melchor
- Gisbert, Javier P.
- Ortega, Miguel A.
- Hernandez-Breijo, Borja
- On Behalf Of The Predicrohn Study Group From Geteccu
Grupos
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 0753-3322, 1950-6007
- Tipo:
- Article
- Páginas:
- 112239-112239
- PubMed:
- 34601192
- Factor de Impacto:
- 1,194 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
BIOMEDICINE & PHARMACOTHERAPY ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Citas Recibidas en Web of Science: 16
Documentos
- No hay documentos
Filiaciones
Keywords
- Adalimumab, IGF-1, Inflammatory bowel diseases
Campos de Estudio
Cita
Guijarro LG,Cano D,Toledo MV,Salinas PS,Chaparro M,Gomez AM,Zoullas S,Rodriguez R,Roman ID,Monasor LS,Ruiz L,del Carmen Boyano M,Guerra I,IBORRA M,Cabriada JL,Bujanda L,Taxonera C,Garcia V,Marin I,Acosta MB,Vera I,Martín MD,Mesonero F,Sempere L,Gomollon F,Hinojosa J,Alvarez M,Gisbert JP,Ortega MA,Hernandez B,On Behalf Of The Predicrohn Study Group From G. Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved. Biomed. Pharmacother. 2021. 144. p. 112239-112239. IF:7,419. (1).