Succinate receptor mediates intestinal inflammation and fibrosis

被引：164

作者：

Macias-Ceja, Dulce C. ^{[1
]}

Ortiz-Masia, Dolores ^{[2
]}

Salvador, Pedro ^{[3
,4
]}

Gisbert-Ferrandiz, Laura ^{[3
,4
]}

Hernandez, Carlos ^{[1
]}

Hausmann, Martin ^{[5
]}

Rogler, Gerhard ^{[5
]}

Esplugues, Juan V. ^{[1
,3
,4
]}

Hinojosa, Joaquin ^{[6
]}

Alos, Rafael ^{[7
]}

Navarro, Francisco ^{[6
]}

Cosin-Roger, Jesus ^{[1
]}

Calatayud, Sara ^{[3
,4
]}

Barrachina, Maria D. ^{[3
,4
]}

机构：

[1] Hosp Dr Peset, FISABIO, Valencia, Spain

[2] Univ Valencia, Fac Med, Dept Med, Valencia, Spain

[3] Univ Valencia, Fac Med, Dept Farmacol, Valencia, Spain

[4] Univ Valencia, Fac Med, CIBER, Valencia, Spain

[5] Univ Zurich, Univ Zurich Hosp, Dept Gastroenterol & Hepatol, Zurich, Switzerland

[6] Hosp Manises, Valencia, Spain

[7] Hosp Sagunto, Valencia, Spain

来源：

MUCOSAL IMMUNOLOGY | 2019年 / 12卷 / 01期

关键词：

GPR91; MACROPHAGES; MECHANISMS; ACTIVATION; AUTOPHAGY; OBESITY; SIGNAL; CELLS;

D O I：

10.1038/s41385-018-0087-3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 alpha-SMA(+) cells in human intestine and we found a positive and significant correlation between SUCNR1 and alpha-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.

引用

页码：178 / 187

页数：10

共 38 条

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