Succinate receptor mediates intestinal inflammation and fibrosis

Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in inflamed areas and its signaling through succinate receptor (SUCNR1) regulates immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease patients and its role in murine intestinal inflammation...

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Detalles Bibliográficos
Autores: Macias-Ceja, Dulce C., Ortiz-Masiá, Dolores, Salvador, Pedro, Gisbert Ferrándiz, Laura, Hernández, Carlos, Hausmann, Martin, Rogler, Gerhard, Esplugues, Juan V., Hinojosa, Joaquín, Alós, Rafael, Navarro, Francisco, Cosin-Roger, Jesus, Calatayud, Sara, Barrachina, María D.
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Católica de Valencia San Vicente Mártir
Repositorio:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Idioma:inglés
OAI Identifier:oai:riucv.ucv.es:20.500.12466/7539
Acceso en línea:https://hdl.handle.net/20.500.12466/7539
Access Level:acceso abierto
Palabra clave:Succinate
Signaling through succinate receptor
Intestinal inflammation
Fibrosis
32 Ciencias Médicas
Descripción
Sumario:Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in inflamed areas and its signaling through succinate receptor (SUCNR1) regulates immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease patients and its role in murine intestinal inflammation and fibrosis. We show that both serum and intestinal succinate levels and SUCNR1 expression in intestinal surgical resections were higher in CD patients than in controls. SUCNR1 co-localized with CD86, CD206, and α-SMA+ cells in human intestine and we found a positive and significant correlation between SUCNR1 and α-SMA expression. In human isolated fibroblasts from CD patients SUCNR1 expression was higher than in those from controls and treatment with succinate increased SUCNR1 expression, fibrotic markers and inflammatory cytokines through SUCNR1. This receptor modulated the expression of pro-inflammatory cytokines in resting murine macrophages, macrophage polarization and fibroblast activation and Sucnr1−/− mice were protected against both acute TNBS-colitis and intestinal fibrosis induced by the heterotopic transplant of colonic tissue. We demonstrate increased succinate levels in serum and SUCNR1 expression in intestinal tissue of CD patients and show a role for SUCNR1 in murine intestinal inflammation and fibrosis.

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