@misc{10481/110740,
year = {2019},
url = {https://hdl.handle.net/10481/110740},
abstract = {Glucocorticoids (GC) are important hormones involved in the regulation of multiple physiological functions.
GC are also widely used antiinflammatory/immunosuppresant drugs. GC are synthesized by the adrenal
cortex as part of the hypothalamus-pituitary-adrenal axis, and also by intestinal epithelial cells, among other
peripheral sites. GC are one of the main therapy choices for the exacerbations of inflammatory bowel
disease, but they are not useful to prolong remission, and development of tolerance with secondary treatment
failure is frequent. Thus GC actions at the intestinal epithelial level are of great importance, both
physiologically and pharmacologically. We generated a tamoxifen inducible NR3C1IEC model to study the
effects of GC on epithelial cells in vivo. Nr3c1 deletion in epithelial cells of the small intestine and colon
was associated with limited colonic inflammation at 1 week postdeletion, involving augmented epithelial
proliferation and mucus production, plus local and systemic immune/inflammatory changes. This phenotype
regressed substantially, but not completely, after 2 weeks. The mechanism may involve augmented
inflammatory signaling by epithelial cells and/or defective barrier function. We conclude that the epithelial
GC receptor plays a significant role in colonic homeostasis in basal conditions, but its deficiency can be
compensated in the short term. Future studies are required to assess the impact of Nr3c1 deletion in other
conditions such as experimental colitis.},
organization = {Ministry of Economy and Competitivity (BFU2014-57736-P, AGL2014-58883-R, SAF2017-88457-R, AGL2017-85270-R), Severo Ochoa Excellence Accreditation (SEV-2016-0644)},
organization = {Fondo Europeo de Desarrollo Regional (FEDER)},
organization = {Junta de Andalucía (CTS235 and CTS164)},
organization = {Ministry of Education},
organization = {Instituto de Salud Carlos III (CIBERehd)},
organization = {Basque Department of Industry, Tourism, and Trade (CIC bioGUNE)},
organization = {Innovation Technology Department of Bizkaia County},
organization = {CIBERehd Network},
organization = {Amino Up Chemical, Pfizer, Hospira, Sanofi, Biosearch Life, Bioiberica and APC Europe},
publisher = {Wiley},
keywords = {Mucosal barrier function},
keywords = {Epithelial homeostasis},
keywords = {Mucus production},
title = {Intestinal epithelial deletion of the glucocorticoid receptor NR3C1 alters expression of inflammatory mediators and barrier function},
doi = {10.1096/fj.201900404RR},
author = {Aranda Clemente, Carlos José and Arredondo-Amador, María and Ocón, Borja and Lavín, José Luis and Aransay, Ana María and Martínez Augustín, María Olga and Sánchez De Medina López-Huertas, Fermín},
}