000112758 001__ 112758
000112758 005__ 20230519145617.0
000112758 0247_ $$2doi$$a10.1016/j.biopha.2021.112239
000112758 0248_ $$2sideral$$a127533
000112758 037__ $$aART-2021-127533
000112758 041__ $$aeng
000112758 100__ $$aGuijarro, Luis G.
000112758 245__ $$aRelationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved
000112758 260__ $$c2021
000112758 5060_ $$aAccess copy available to the general public$$fUnrestricted
000112758 5203_ $$aInflammatory 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
000112758 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/12-02557$$9info:eu-repo/grantAgreement/ES/ISCIII/PI13-00041
000112758 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000112758 590__ $$a7.419$$b2021
000112758 592__ $$a1.194$$b2021
000112758 594__ $$a11.6$$b2021
000112758 591__ $$aPHARMACOLOGY & PHARMACY$$b26 / 279 = 0.093$$c2021$$dQ1$$eT1
000112758 593__ $$aPharmacology$$c2021$$dQ1
000112758 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b30 / 140 = 0.214$$c2021$$dQ1$$eT1
000112758 593__ $$aMedicine (miscellaneous)$$c2021$$dQ1
000112758 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000112758 700__ $$aCano-Martínez, David
000112758 700__ $$aToledo-Lobo, M.Val
000112758 700__ $$aSalinas, Patricia Sanmartín
000112758 700__ $$aChaparro, María
000112758 700__ $$aGómez-Lahoz, Ana M.
000112758 700__ $$aZoullas, Sofía
000112758 700__ $$aRodríguez-Torres, Rosa
000112758 700__ $$aRomán, Irene D.
000112758 700__ $$aMonasor, Laura Sebastián
000112758 700__ $$aRuiz-Llorente, Lidia
000112758 700__ $$adel Carmen Boyano-Adánez, María
000112758 700__ $$aGuerra, Iván
000112758 700__ $$aIborra, Marisa
000112758 700__ $$aCabriada, José Luis
000112758 700__ $$aBujanda, Luis
000112758 700__ $$aTaxonera, Carlos
000112758 700__ $$aGarcía-Sánchez, Valle
000112758 700__ $$aMarín-Jiménez, Ignacio
000112758 700__ $$aAcosta, Manuel Barreiro-de
000112758 700__ $$aVera, Isabel
000112758 700__ $$aMartín-Arranz, María Dolores
000112758 700__ $$aMesonero, Francisco
000112758 700__ $$aSempere, Laura
000112758 700__ $$0(orcid)0000-0003-0076-3529$$aGomollón, Fernando$$uUniversidad de Zaragoza
000112758 700__ $$aHinojosa, Joaquín
000112758 700__ $$aAlvarez-Mon, Melchor
000112758 700__ $$aGisbert, Javier P.
000112758 700__ $$aOrtega, Miguel A.
000112758 700__ $$aHernández-Breijo, Borja
000112758 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000112758 773__ $$g144 (2021), 112239 [12 pp.]$$pBiomed. pharmacother.$$tBIOMEDICINE & PHARMACOTHERAPY$$x0753-3322
000112758 8564_ $$s5412219$$uhttps://zaguan.unizar.es/record/112758/files/texto_completo.pdf$$yVersión publicada
000112758 8564_ $$s2491460$$uhttps://zaguan.unizar.es/record/112758/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000112758 909CO $$ooai:zaguan.unizar.es:112758$$particulos$$pdriver
000112758 951__ $$a2023-05-18-16:12:06
000112758 980__ $$aARTICLE