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

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dc.contributor.authorLandskron, Glauben
dc.contributor.authorDubois-Camacho, Karen
dc.contributor.authorOrellana-Serradell, Octavio
dc.contributor.authorDe la Fuente, Marjorie
dc.contributor.authorParada-Venegas, Daniela
dc.contributor.authorBitrán, Mirit
dc.contributor.authorDiaz-Jimenez, David
dc.contributor.authorTang, Shuang
dc.contributor.authorCidlowski, John A.
dc.contributor.authorLi, Xiaoling
dc.contributor.authorMolina, Hector
dc.contributor.authorGonzalez, Carlos M.
dc.contributor.authorSimian, Daniela
dc.contributor.authorLubascher, Jaime
dc.contributor.authorPola, Victor
dc.contributor.authorMontecino, Martín
dc.contributor.authorBlokzijl, Tjasso
dc.contributor.authorFaber, Klaas Nico
dc.contributor.authorGonzález, María-Julieta
dc.contributor.authorQuera, Rodrigo
dc.contributor.authorHermoso, Marcela A.
dc.date.accessioned2024-04-29T15:54:40Z
dc.date.available2024-04-29T15:54:40Z
dc.date.issued2022-06-02
dc.descriptionIndexación: Scopus.
dc.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 (GRβ) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GRiKO) 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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
dc.description.urihttps://www.mdpi.com/2073-4409/11/12/1905
dc.identifier.citationCells, Volume 11, Issue 12, June-2 2022, Article number 1905
dc.identifier.doi10.3390/cells11121905
dc.identifier.issn2073-4409
dc.identifier.urihttps://repositorio.unab.cl/handle/ria/56445
dc.language.isoen
dc.publisherMDPI
dc.rights.licenseCC BY 4.0 DEED Atribución 4.0 Internacional
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectGlucocorticoid receptor
dc.subjectLRH-1
dc.subjectSteroid dependency
dc.subjectSteroid refractoriness
dc.subjectUlcerative colitis
dc.titleRegulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitis
dc.title.alternativeMDPI
dc.typeAnimaAnimacióntion
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