Regulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitis

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dc.coverageDOI: 10.3390/cells11121905
dc.creatorLandskron, Glauben
dc.creatorDubois-Camacho, Karen
dc.creatorOrellana-Serradell, Octavio
dc.creatorDe la Fuente, Marjorie
dc.creatorParada-Venegas, Daniela
dc.creatorBitrán, Mirit
dc.creatorDiaz-Jimenez, David
dc.creatorTang, Shuang
dc.creatorCidlowski, John A.
dc.creatorLi, Xiaoling
dc.creatorMolina, Hector
dc.creatorGonzalez, Carlos M.
dc.creatorSimian, Daniela
dc.creatorLubascher, Jaime
dc.creatorPola, Victor
dc.creatorMontecino, Martín
dc.creatorBlokzijl, Tjasso
dc.creatorFaber, Klaas Nico
dc.creatorGonzález, María Julieta
dc.creatorQuera, Rodrigo
dc.creatorHermoso, Marcela A.
dc.date2022
dc.date.accessioned2025-11-18T19:42:02Z
dc.date.available2025-11-18T19:42:02Z
dc.description<p>Ulcerative 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 (GRβ) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GR<sup>iKO</sup>) 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.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/533fda55-3cf4-4630-a406-73f75c0e5c83
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/52127
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.11 (2022) date: 2022-06-12 nr.12
dc.subjectAnimals
dc.subjectColitis, Ulcerative/drug therapy
dc.subjectGlucocorticoids/metabolism
dc.subjectHumans
dc.subjectIntestinal Mucosa/metabolism
dc.subjectIntestines
dc.subjectMice
dc.subjectSteroids/metabolism
dc.titleRegulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitiseng
dc.typeArticleeng
dc.typeArtículospa
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