Irene D Román1, David Cano-Martínez1, María Val T Lobo2, María Dolores Fernández-Moreno1, Borja Hernández-Breijo1, Silvia Sacristán3, Patricia Sanmartín-Salinas1, Jorge Monserrat4, Javier P Gisbert5, Luis G Guijarro1. 1. a Department of Systems Biology , Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Alcalá , Alcalá de Henares , Spain. 2. b Department of Biomedicine and Biotechnology , University of Alcalá , Alcalá de Henares , Spain. 3. c Instituto Ramón y Cajal de Investigación Sanitaria (IRyCIS) , Madrid , Spain. 4. d Department of Medicine , University of Alcalá , Alcalá de Henares , Spain. 5. e Gastroenterology Unit , Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) , Madrid , Spain.
Abstract
OBJECTIVE: Our purpose was to study the molecular basis of infliximab (IFX) effect on colon mucosa in a colitis model and to identify new biomarkers of mucosal healing. METHODS: Healthy rats and rats which were subjected to experimental colitis induced by dextran sulfate sodium, with or without IFX treatment (in the short- and long-term), were studied along with forty-seven IBD patients. Colon mucosal integrity by periodic acid Schiff (PAS) staining, intestinal damage by immunohistochemistry (proliferating cell nuclear antigen, β-catenin, E-cadherin, phosphotyrosine, p-p38, allograft inflammatory factor-1 (AIF-1) and colonic mucosal apoptosis by TUNEL staining were evaluated in rats while serum and colon AIF-1 levels were determined in IBD patients. RESULTS: In rats with colitis, IFX reestablished the epithelial barrier integrity, recovered mucus production and decreased colon inflammation, as verified by reduced serum and colon AIF-1 levels; colon and serum AIF-1 levels were also lower in inactive IBD patients compare to active ones. P38 activation after IFX treatment tended to induce differentiation/proliferation of epithelial cells along the colonic crypt-villous axis. CONCLUSIONS: These findings support AIF-1 as a new biomarker of mucosal healing in experimental colitis and suggest that p38 activation is involved in the mucosal healing intracellular mechanism induced by IFX treatment.
OBJECTIVE: Our purpose was to study the molecular basis of infliximab (IFX) effect on colon mucosa in a colitis model and to identify new biomarkers of mucosal healing. METHODS: Healthy rats and rats which were subjected to experimental colitis induced by dextran sulfate sodium, with or without IFX treatment (in the short- and long-term), were studied along with forty-seven IBDpatients. Colon mucosal integrity by periodic acid Schiff (PAS) staining, intestinal damage by immunohistochemistry (proliferating cell nuclear antigen, β-catenin, E-cadherin, phosphotyrosine, p-p38, allograft inflammatory factor-1 (AIF-1) and colonic mucosal apoptosis by TUNEL staining were evaluated in rats while serum and colon AIF-1 levels were determined in IBDpatients. RESULTS: In rats with colitis, IFX reestablished the epithelial barrier integrity, recovered mucus production and decreased colon inflammation, as verified by reduced serum and colon AIF-1 levels; colon and serum AIF-1 levels were also lower in inactive IBDpatients compare to active ones. P38 activation after IFX treatment tended to induce differentiation/proliferation of epithelial cells along the colonic crypt-villous axis. CONCLUSIONS: These findings support AIF-1 as a new biomarker of mucosal healing in experimental colitis and suggest that p38 activation is involved in the mucosal healing intracellular mechanism induced by IFX treatment.
Authors: Patricia Sanmartín-Salinas; M Val Toledo-Lobo; Fernando Noguerales-Fraguas; María-Encarnación Fernández-Contreras; Luis G Guijarro Journal: J Mol Histol Date: 2017-11-28 Impact factor: 2.611
Authors: Patricia Sanmartín-Salinas; María Del Val Toledo Lobo; Fernando Noguerales-Fraguas; Miguel Toro Londoño; Antonio Jiménez-Ruiz; Luis Gonzalez Guijarro Journal: J Gastroenterol Date: 2018-01-20 Impact factor: 7.527
Authors: Rodrigo B Mansur; Francheska Delgado-Peraza; Mehala Subramaniapillai; Yena Lee; Michelle Iacobucci; Flora Nasri; Nelson Rodrigues; Joshua D Rosenblat; Elisa Brietzke; Victoria E Cosgrove; Nicole E Kramer; Trisha Suppes; Charles L Raison; Andrea Fagiolini; Natalie Rasgon; Sahil Chawla; Carlos Nogueras-Ortiz; Dimitrios Kapogiannis; Roger S McIntyre Journal: J Psychiatr Res Date: 2020-12-04 Impact factor: 4.791
Authors: Carmen Rubio; Marta Puerto; Juan J García-Rodríquez; Van B Lu; Irma García-Martínez; Rosa Alén; Patricia Sanmartín-Salinas; M Val Toledo-Lobo; Jorge Saiz; Javier Ruperez; Coral Barbas; Luis Menchén; Fiona M Gribble; Frank Reimann; Luis G Guijarro; Jose M Carrascosa; Ángela M Valverde Journal: Mol Metab Date: 2020-02-06 Impact factor: 7.422
Authors: Luis G Guijarro; David Cano-Martínez; M Val Toledo-Lobo; Lidia Ruiz-Llorente; María Chaparro; 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; Sofía Zoullas; Jorge Monserrat; Cesar Menor-Salvan; Melchor Alvarez-Mon; Javier P Gisbert; Miguel A Ortega; Borja Hernández-Breijo Journal: Biomedicines Date: 2022-03-21