Resistin-like molecule β regulates innate colonic function:: Barrier integrity and inflammation susceptibility
Resistin-like molecule β regulates innate colonic function:: Barrier integrity and inflammation susceptibility
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DOI：
10.1016/j.jaci.2006.04.039
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发表时间：
2006-07-01
影响因子：
14.2
通讯作者：
Rothenberg, Marc E.
中科院分区：
文献类型：
--
作者：
Hogan, Simon P.;Seidu, Luqman;Rothenberg, Marc E.
背景：抵抗素样分子（RELM）β是一种在胃肠道表达的富含半胱氨酸的细胞因子，与胰岛素抵抗和胃肠道线虫免疫有关；然而，其功能主要仍然是个谜。
目的：我们试图阐明RELM -β在胃肠道中的功能。
方法：我们构建了RELM -β基因靶向小鼠，并检测了结肠上皮屏障功能、基因表达谱以及对急性结肠炎症的易感性。
结果：我们发现RELM -β由杯状细胞和肠上皮细胞在结肠中组成性表达，并且在体内平衡中起作用，这通过在缺乏RELM -β时结肠mRNA转录本和上皮屏障功能的改变来评估。利用急性结肠炎症模型，我们证明RELM -β在调节结肠炎症易感性方面起核心作用。机制研究确定RELM -β调节III型再生基因（REG）（REG3β和γ）的表达，这些分子已知会影响核因子κB信号传导。
结论：这些数据确定了RELM -β在维持结肠屏障功能和胃肠道先天免疫中的关键作用。
临床意义：这些发现确定RELM -β是胃肠道稳态功能和结肠炎症中的一种重要分子，因此，这些结果对多种人类炎症性胃肠道疾病，包括过敏性胃肠病具有影响。
Background: Resistin-like molecule (RELM) P is a cysteine-rich cytokine expressed in the gastrointestinal tract and implicated in insulin resistance and gastrointestinal nematode immunity; however, its function primarily remains an enigma.Objective: We sought to elucidate the function of RELM-beta in the gastrointestinal tract.Methods: We generated RELM-beta gene-targeted mice and examined colonic epithelial barrier function, gene expression profiles, and susceptibility to acute colonic inflammation.Results: We show that RELM-P is constitutively expressed in the colon by goblet cells and enterocytes and has a role in homeostasis, as assessed by alterations in colon mRNA transcripts and epithelial barrier function in the absence of RELM-P. Using acute colonic inflammatory models, we demonstrate that RELM-beta has a central role in the regulation of susceptibility to colonic inflammation. Mechanistic studies identify that RELM-beta regulates expression of type III regenerating gene (REG) (REG3 beta and gamma), molecules known to influence nuclear factor kappa B signaling.Conclusions: These data define a critical role for RELM-P in the maintenance of colonic barrier function and gastrointestinal innate immunity.Clinical implications: These findings identify RFLM-beta as an important molecule in homeostatic gastrointestinal function and colonic inflammation, and as such, these results have implications for a variety of human inflammatory gastrointestinal conditions, including allergic gastroenteropathies.