Vitamin D and Wnt3A have additive and partially overlapping modulatory effects on gene expression and phenotype in human colon fibroblasts

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dc.contributor.author Ferrer-Mayorga, Gemma
dc.contributor.author Niell, Núria
dc.contributor.author Cantero, Ramón
dc.contributor.author González-Sancho, José Manuel
dc.contributor.author del Peso, Luis
dc.contributor.author Muñoz, Alberto
dc.contributor.author Larriba, María Jesús
dc.contributor.other UAM. Departamento de Biología es_ES
dc.date.accessioned 2020-05-06T10:17:43Z
dc.date.available 2020-05-06T10:17:43Z
dc.date.issued 2019-12-01
dc.identifier.citation Scientific Reports 2019.9 (2019): 8085 en_US
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10486/690985
dc.description.abstract The Wnt/β-catenin signalling pathway is essential for intestinal epithelium homeostasis, but its aberrant activation is a hallmark of colorectal cancer (CRC). Several studies indicate that the bioactive vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes epithelial differentiation of colon carcinoma cells in part through antagonism of the Wnt/β-catenin pathway. It is now accepted that stromal fibroblasts are crucial in healthy and pathologic intestine: pericryptal myofibroblasts are constituents of the stem cell niche and cancer-associated fibroblasts (CAFs) contribute to CRC progression. However, studies on the combined action of 1,25(OH)2D3 and Wnt factors in colon fibroblasts are lacking. Here we show by global transcriptomic studies that 1,25(OH)2D3 and Wnt3A have profound, additive, partially overlapping effects on the gene expression profile of CCD-18Co human colon myofibroblasts. Moreover, 1,25(OH)2D3 and Wnt3A inhibit CCD-18Co cell proliferation and migration, while 1,25(OH)2D3 reduces, but Wnt3A increases, their capacity to contract collagen gels (a marker of fibroblast activation). These data were largely confirmed in patient-derived primary colon normal fibroblasts and CAFs, and in fibroblasts from other origins. Our results indicate that 1,25(OH)2D3 and Wnt3A are strong regulators of colon fibroblast biology and contribute to a better knowledge of intestinal homeostasis and stromal fibroblast action in CRC en_US
dc.description.sponsorship The work in the authors’ laboratories is supported by the Spanish Ministerio de Ciencia, Innovación y Universidades - Fondo Europeo de Desarrollo Regional (FEDER) (SAF2016-76377-R, SAF2017-90604-REDT), Consejo Superior de Investigaciones Científicas (201820I058), and Instituto de Salud Carlos III - FEDER (CIBERONC, CB16/12/00273; CIBERES, CB15/00037) en_US
dc.format.extent 13 pag. en_US
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Nature Publishing Group en_US
dc.relation.ispartof Scientific Reports en_US
dc.rights © 2019, The Author(s) en_US
dc.subject.other Intestinal epithelium en_US
dc.subject.other Homeostasis en_US
dc.subject.other Wnt/β-catenin en_US
dc.subject.other Colorectal cancer (CRC) en_US
dc.title Vitamin D and Wnt3A have additive and partially overlapping modulatory effects on gene expression and phenotype in human colon fibroblasts en_US
dc.type article en
dc.subject.eciencia Biología y Biomedicina / Biología es
dc.relation.publisherversion https://doi.org/10.1038/s41598-019-44574-9
dc.identifier.doi 10.1038/s41598-019-44574-9
dc.identifier.publicationfirstpage 8085-1
dc.identifier.publicationissue 9
dc.identifier.publicationlastpage 8085-13
dc.identifier.publicationvolume 2019
dc.relation.projectID Gobierno de España. SAF2016-76377-R es_ES
dc.relation.projectID Gobierno de España. SAF2017-90604-REDT es_ES
dc.relation.projectID Gobierno de España. CB16/12/00273 es_ES
dc.relation.projectID Gobierno de España. CB15/00037 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Niell Garolera, Nuria (278877)
dc.authorUAM González Sancho, José Manuel (261056)


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