Succinate receptor mediates intestinal inflammation and fibrosis - PubMed (original) (raw)

. 2019 Jan;12(1):178-187.

doi: 10.1038/s41385-018-0087-3. Epub 2018 Oct 2.

Dolores Ortiz-Masiá # 2, Pedro Salvador 3, Laura Gisbert-Ferrándiz 3, Carlos Hernández 1, Martin Hausmann 4, Gerhard Rogler 4, Juan V Esplugues 1 3, Joaquín Hinojosa 5, Rafael Alós 6, Francisco Navarro 5, Jesus Cosin-Roger 7, Sara Calatayud # 3, María D Barrachina # 3

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Succinate receptor mediates intestinal inflammation and fibrosis

Dulce C Macias-Ceja et al. Mucosal Immunol. 2019 Jan.

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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.

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References

    1. Wynn, T. A. & Ramalingam, T. R. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat. Med. 18, 1028–1040 (2012). - DOI
    1. Rieder, F., Zimmermann, E. M., Remzi, F. H. & Sandborn, W. J. Crohn’s disease complicated by strictures: a systematic review. Gut 62, 1072–1084 (2013). - DOI
    1. Li, C. & Kuemmerle, J. F. Mechanisms that mediate the development of fibrosis in patients with Crohn’s disease. Inflam. Bowel Dis. 20, 1250–1258 (2014). - DOI
    1. Rieder, F., Fiocchi, C. & Rogler, G. Mechanisms, management, and treatment of fibrosis in patients with inflammatory bowel diseases. Gastroenterology 152, 340–350 e346 (2017). - DOI
    1. Mills, E. & O’neill, L. A. Succinate: a metabolic signal in inflammation. Trends Cell Biol. 24, 313–320 (2014). - DOI

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