Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved

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...

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Autores principales:	Luis G. Guijarro, David Cano-Martínez, M.Val Toledo-Lobo, Patricia Sanmartín Salinas, María Chaparro, Ana M. Gómez-Lahoz, Sofía Zoullas, Rosa Rodríguez-Torres, Irene D. Román, Laura Sebastián Monasor, Lidia Ruiz-Llorente, María del Carmen Boyano-Adánez, Iván Guerra, Marisa Iborra, José Luis Cabriada, Luis Bujanda, Carlos Taxonera, Valle García-Sánchez, Ignacio Marín-Jiménez, Manuel Barreiro-de Acosta, Isabel Vera, María Dolores Martín-Arranz, Francisco Mesonero, Laura Sempere, Fernando Gomollón, Joaquín Hinojosa, Melchor Alvarez-Mon, Javier P. Gisbert, Miguel A. Ortega, Borja Hernández-Breijo, on behalf of the PREDICROHN study group from GETECCU
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	IGF-1 Inflammatory bowel diseases Adalimumab Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/07a4ccf32ca74a43a9db582d7fa13f0a
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spelling	oai:doaj.org-article:07a4ccf32ca74a43a9db582d7fa13f0a2021-11-14T04:28:45ZRelationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved0753-332210.1016/j.biopha.2021.112239https://doaj.org/article/07a4ccf32ca74a43a9db582d7fa13f0a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010234https://doaj.org/toc/0753-3322Inflammatory 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.Luis G. GuijarroDavid Cano-MartínezM.Val Toledo-LoboPatricia Sanmartín SalinasMaría ChaparroAna M. Gómez-LahozSofía ZoullasRosa Rodríguez-TorresIrene D. RománLaura Sebastián MonasorLidia Ruiz-LlorenteMaría del Carmen Boyano-AdánezIván GuerraMarisa IborraJosé Luis CabriadaLuis BujandaCarlos TaxoneraValle García-SánchezIgnacio Marín-JiménezManuel Barreiro-de AcostaIsabel VeraMaría Dolores Martín-ArranzFrancisco MesoneroLaura SempereFernando GomollónJoaquín HinojosaMelchor Alvarez-MonJavier P. GisbertMiguel A. OrtegaBorja Hernández-Breijo on behalf of the PREDICROHN study group from GETECCUElsevierarticleIGF-1Inflammatory bowel diseasesAdalimumabTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112239- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	IGF-1 Inflammatory bowel diseases Adalimumab Therapeutics. Pharmacology RM1-950
spellingShingle	IGF-1 Inflammatory bowel diseases Adalimumab Therapeutics. Pharmacology RM1-950 Luis G. Guijarro David Cano-Martínez M.Val Toledo-Lobo Patricia Sanmartín Salinas María Chaparro Ana M. Gómez-Lahoz Sofía Zoullas Rosa Rodríguez-Torres Irene D. Román Laura Sebastián Monasor Lidia Ruiz-Llorente María del Carmen Boyano-Adánez Iván Guerra Marisa Iborra José Luis Cabriada Luis Bujanda Carlos Taxonera Valle García-Sánchez Ignacio Marín-Jiménez Manuel Barreiro-de Acosta Isabel Vera María Dolores Martín-Arranz Francisco Mesonero Laura Sempere Fernando Gomollón Joaquín Hinojosa Melchor Alvarez-Mon Javier P. Gisbert Miguel A. Ortega Borja Hernández-Breijo on behalf of the PREDICROHN study group from GETECCU Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved
description	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.
format	article
author	Luis G. Guijarro David Cano-Martínez M.Val Toledo-Lobo Patricia Sanmartín Salinas María Chaparro Ana M. Gómez-Lahoz Sofía Zoullas Rosa Rodríguez-Torres Irene D. Román Laura Sebastián Monasor Lidia Ruiz-Llorente María del Carmen Boyano-Adánez Iván Guerra Marisa Iborra José Luis Cabriada Luis Bujanda Carlos Taxonera Valle García-Sánchez Ignacio Marín-Jiménez Manuel Barreiro-de Acosta Isabel Vera María Dolores Martín-Arranz Francisco Mesonero Laura Sempere Fernando Gomollón Joaquín Hinojosa Melchor Alvarez-Mon Javier P. Gisbert Miguel A. Ortega Borja Hernández-Breijo on behalf of the PREDICROHN study group from GETECCU
author_facet	Luis G. Guijarro David Cano-Martínez M.Val Toledo-Lobo Patricia Sanmartín Salinas María Chaparro Ana M. Gómez-Lahoz Sofía Zoullas Rosa Rodríguez-Torres Irene D. Román Laura Sebastián Monasor Lidia Ruiz-Llorente María del Carmen Boyano-Adánez Iván Guerra Marisa Iborra José Luis Cabriada Luis Bujanda Carlos Taxonera Valle García-Sánchez Ignacio Marín-Jiménez Manuel Barreiro-de Acosta Isabel Vera María Dolores Martín-Arranz Francisco Mesonero Laura Sempere Fernando Gomollón Joaquín Hinojosa Melchor Alvarez-Mon Javier P. Gisbert Miguel A. Ortega Borja Hernández-Breijo on behalf of the PREDICROHN study group from GETECCU
author_sort	Luis G. Guijarro
title	Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved
title_short	Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved
title_full	Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved
title_fullStr	Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved
title_full_unstemmed	Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved
title_sort	relationship between igf-1 and body weight in inflammatory bowel diseases: cellular and molecular mechanisms involved
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/07a4ccf32ca74a43a9db582d7fa13f0a
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Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved

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