IFN?-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn's Disease

Background: Fibrosis is a common complication of Crohn's disease (CD) in which macrophages play a central role. Epithelial-mesenchymal transition (EMT) and the WNT pathway have been associated with fibrosis. We aim to analyse the relevance of the tissue microenvironment in macrophage phenotype...

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Detalles Bibliográficos
Autores: Macias-Ceja DC, Coll S, Bauset C, Seco-Cervera M, Gisbert-Ferrándiz L, Navarro F, Cosin-Roger J, Calatayud S, Barrachina MD, Ortiz-Masia D
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p13656
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/13656
Access Level:acceso abierto
Palabra clave:Crohn disease
IFN gamma
Epithelial Mesenchymal Transition (EMT)
macrophages
fibrosis
Descripción
Sumario:Background: Fibrosis is a common complication of Crohn's disease (CD) in which macrophages play a central role. Epithelial-mesenchymal transition (EMT) and the WNT pathway have been associated with fibrosis. We aim to analyse the relevance of the tissue microenvironment in macrophage phenotype and the EMT process. Methods: Intestinal surgical resections are obtained from control and CD patients with stenotic or penetrating behaviour. Cytokine's expression, macrophage phenotype, EMT markers and WNT signalling pathway are determined by WB, RT-PCR, ELISA or Cytometry. U937 cells are treated with IFN gamma, TNF alpha, IL1 beta, IL4 or IL10 and co-cultured with HT29 cells and, in some cases, are treated with XAV939 or miFZD4. The expression of macrophage, EMT and WNT pathway markers in U937 or HT29 cells is analysed by WB or RT-PCR. Results: IFN gamma, WNT6, CD16 and CD86 are increased in the intestinal tissue of CD patients. IFN gamma-treated U937 activated the EMT process and WNT pathway in HT29 cells, and the EMT process is mediated by FZD4. Conclusions: An IFN gamma-rich microenvironment polarises macrophages, which induces EMT through the WNT pathway.