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Authordc.contributor.authorLandskron Ramos, Glauben Tamara
Authordc.contributor.authorDubois Camacho, Karen
Authordc.contributor.authorOrellana Serradell, Octavio Andrés
Authordc.contributor.authorFuente López, Majorie de la
Authordc.contributor.authorParada Venegas, Daniela Estefani
Authordc.contributor.authorBitrán Ambler, Mirit Luisa
Authordc.contributor.authorDíaz Jiménez, David
Authordc.contributor.authorTang, Shuang
Authordc.contributor.authorCidlowski, John A.
Authordc.contributor.authorLi, Xiaoling
Authordc.contributor.authorMolina, Héctor
Authordc.contributor.authorGonzález, Carlos M.
Authordc.contributor.authorSimian, Daniela
Authordc.contributor.authorLubascher, Jaime
Authordc.contributor.authorPola, Víctor
Authordc.contributor.authorMontecino, Martín
Authordc.contributor.authorBlokzijl, Tjasso
Authordc.contributor.authorFaber, Klaas Nico
Authordc.contributor.authorGonzález Burgos, María Julieta
Authordc.contributor.authorQuera, Rodrigo
Authordc.contributor.authorHermoso, Marcela Alejandra
Admission datedc.date.accessioned2022-08-10T19:45:07Z
Available datedc.date.available2022-08-10T19:45:07Z
Publication datedc.date.issued2022
Cita de ítemdc.identifier.citationCells 2022, 11, 1905es_ES
Identifierdc.identifier.other10.3390/cells11121905
Identifierdc.identifier.urihttps://repositorio.uchile.cl/handle/2250/187262
Abstractdc.description.abstractUlcerative colitis (UC) is an inflammatory bowel disease (IBD) and can be treated with glucocorticoids (GC), although some patients are unresponsive to this therapy. The transcription factor LRH-1/NR5A2 is critical to intestinal cortisol production (intestinal steroidogenesis), being reduced in UC patients. However, the relationship between LRH-1 expression and distribution with altered corticosteroid responses is unknown. To address this, we categorized UC patients by their steroid response. Here, we found that steroid-dependent and refractory patients presented reduced glucocorticoid receptor (GR)-mediated intestinal steroidogenesis compared to healthy individuals and responder patients, possibly related to increased colonic mucosa GR isoform beta (GR beta) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GR(iKO)) dextran sodium sulfate (DSS)-colitis mice model presented decreased epithelial LRH-1 expression, whilst it increased in the lamina propria compared to DSS-treated control mice. Mechanistically, GR directly induced NR5A2 gene expression in CCD841CoN cells and human colonic organoids. Furthermore, GR bound to two glucocorticoid-response elements within the NR5A2 promoter in dexamethasone-stimulated CCD841CoN cells. We conclude that GR contributes to intestinal steroidogenesis by inducing LRH-1 in epithelial cells, suggesting LRH-1 as a potential marker for glucocorticoid-impaired response in UC. However, further studies with a larger patient cohort will be necessary to confirm role of LRH-1 as a therapeutic biomarker.es_ES
Patrocinadordc.description.sponsorshipNational Agency of Research and Development ANID/FONDECYT 1170648 1220702 11190990 3190931 3210367 ICBM2021_ 570333 ANID/FONDAP 15090007 Glucocorticoid hormone action 1ZIA ES090057 24 Apoptosis 1ZIA ES090079 24 Molecular genetics support to identify gene/environment interactions in disease 1ZIC ES102546 12 Intramural Research Program of National Institute of Environmental Health Sciences of the NIH Z01 ES102205 Vice-Rector's Office for Academic Affairs, Postgraduate and Postgraduate Department, Universidad de Chilees_ES
Lenguagedc.language.isoenes_ES
Publisherdc.publisherMDPIes_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
Sourcedc.sourceCellses_ES
Keywordsdc.subjectLRH-1es_ES
Keywordsdc.subjectGlucocorticoid receptores_ES
Keywordsdc.subjectUlcerative colitises_ES
Keywordsdc.subjectSteroid refractorinesses_ES
Keywordsdc.subjectSteroid dependencyes_ES
Títulodc.titleRegulation of the intestinal extra-adrenal steroidogenic pathway component LRH-1 by glucocorticoids in ulcerative colitises_ES
Document typedc.typeArtículo de revistaes_ES
dc.description.versiondc.description.versionVersión publicada - versión final del editores_ES
dcterms.accessRightsdcterms.accessRightsAcceso abiertoes_ES
Catalogueruchile.catalogadorapces_ES
Indexationuchile.indexArtículo de publícación WoSes_ES


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Attribution-NonCommercial-NoDerivs 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States