Vitamin D and Wnt3A have additive and partially overlapping modulatory effects on gene expression and phenotype in human colon fibroblasts
Entidad
UAM. Departamento de BiologíaEditor
Nature Publishing GroupFecha de edición
2019-12-01Cita
10.1038/s41598-019-44574-9
Scientific Reports 2019.9 (2019): 8085
ISSN
2045-2322DOI
10.1038/s41598-019-44574-9Financiado por
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)Proyecto
Gobierno de España. SAF2016-76377-R; Gobierno de España. SAF2017-90604-REDT; Gobierno de España. CB16/12/00273; Gobierno de España. CB15/00037Versión del editor
https://doi.org/10.1038/s41598-019-44574-9Materias
Intestinal epithelium; Homeostasis; Wnt/β-catenin; Colorectal cancer (CRC); Biología y Biomedicina / BiologíaDerechos
© 2019, The Author(s)Resumen
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
Lista de ficheros
Google Scholar:Ferrer-Mayorga, Gemma
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Niell, Núria
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Cantero Cid, Ramón
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González Sancho, José Manuel
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del Peso, Luis
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Muñoz, Alberto
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Larriba, María Jesús
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