The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases.,Mucosal Immunology

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The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-Dec-12 , DOI: 10.1038/s41385-018-0119-z
M Body-Malapel ₁ , M Djouina ₁ , C Waxin ₁ , A Langlois ₁ , C Gower-Rousseau ₁ , P Zerbib _{1,

2} , A-M Schmidt ₃ , P Desreumaux ₁ , E Boulanger ₁ , C Vignal ₁

Affiliation

Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions of the intestinal tract. IBD are believed to result from an inappropriate immune response against the intestinal flora in genetically predisposed patients. The precise etiology of these diseases is not fully understood, therefore treatments rely on the dampening of symptoms, essentially inflammation, rather than on the cure of the disease. Despite the availability of biologics, such as anti-TNF antibodies, some patients remain in therapeutic failure and new treatments are thus needed. The multiligand receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in inflammatory reactions and immune system activation. Here, we investigated the role of RAGE in intestinal inflammation and its potential as a therapeutic target in IBD. We showed that RAGE was upregulated in inflamed tissues from IBD patients compared to controls. Rage^-/- mice were less susceptible to intestinal and colonic inflammation development than WT mice. WT mice treated with the RAGE-specific inhibitor FPS-ZM1 experienced less severe enteritis and colitis. We demonstrated that RAGE could induce intestinal inflammation by promoting oxidative stress and endothelial activation which were diminished by FPS-ZM1 treatment. Our results revealed the RAGE signaling pathway as a promising therapeutic target for IBD patients.

中文翻译：

RAGE 信号通路与肠道炎症有关，是炎症性肠病的一个有前途的治疗靶点。

炎症性肠病 (IBD) 是肠道的慢性炎症性疾病。IBD 被认为是由遗传易感患者对肠道菌群的不适当免疫反应引起的。这些疾病的确切病因尚不完全清楚，因此治疗依赖于症状的抑制，主要是炎症，而不是疾病的治愈。尽管可以使用抗 TNF 抗体等生物制剂，但一些患者仍处于治疗失败状态，因此需要新的治疗方法。晚期糖基化终产物 (RAGE) 的多配体受体是一种模式识别受体，与炎症反应和免疫系统激活有关。在这里，我们研究了 RAGE 在肠道炎症中的作用及其作为 IBD 治疗靶点的潜力。我们发现，与对照组相比，RAGE 在 IBD 患者的发炎组织中上调。愤怒^-/-与 WT 小鼠相比，小鼠对肠道和结肠炎症发展的敏感性较低。用 RAGE 特异性抑制剂 FPS-ZM1 治疗的 WT 小鼠经历了较轻的肠炎和结肠炎。我们证明了 RAGE 可以通过促进氧化应激和内皮细胞激活来诱导肠道炎症，而 FPS-ZM1 治疗可以减少这些炎症。我们的结果揭示了 RAGE 信号通路作为 IBD 患者的有前途的治疗靶点。

更新日期：2019-01-26

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