琥珀酸受体或是治疗IBD的新靶点

创作:Cherry 审核:mildbreeze 10月11日
琥珀酸聚集在炎症区域,通过琥珀酸受体SUCNR1调节免疫;
克罗恩病(CD)患者的血清和肠道琥珀酸水平上升,肠组织和成纤维细胞中琥珀酸受体SUCNR1表达增加,SUCNR1与肠纤维化标志物α-SMA的表达正相关、与CD86、CD206和α-SMA+细胞共存;
SUCNR1介导巨噬中促炎因子的表达、巨噬细胞极化和成纤维细胞活化,敲除SUNCR1可使小鼠抵抗实验诱导的抗结肠炎和肠纤维化;
CD患者肠道中,SUCNR1信号可加剧炎症和纤维化,有望成为新的CD药物靶点。
延伸阅读
Mucosal Immunology [IF:7.36]

Succinate receptor mediates intestinal inflammation and fibrosis

琥珀酸受体介导肠道炎症和纤维化

10-02, Article, 10.1038/s41385-018-0087-3more

Abstract:
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.

First Authors:
Dulce C Macias-Ceja,Dolores Ortiz-Masiá,Sara Calatayud,María D Barrachina

Correspondence Authors:
Jesus Cosin-Roger

All Authors:
Dulce C Macias-Ceja,Dolores Ortiz-Masiá,Pedro Salvador,Laura Gisbert-Ferrándiz,Carlos Hernández,Martin Hausmann,Gerhard Rogler,Juan V Esplugues,Joaquín Hinojosa,Rafael Alós,Francisco Navarro,Jesus Cosin-Roger,Sara Calatayud,María D Barrachina