Butyrate ameliorated-NLRC3 protects the intestinal barrier in a GPR43-dependent manner
Butyrate ameliorated-NLRC3 protects the intestinal barrier in a GPR43-dependent manner
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DOI：
10.1016/j.yexcr.2018.04.018
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发表时间：
2018-07-01
影响因子：
3.7
通讯作者：
Yu, Tao
中科院分区：
文献类型：
--
作者：
Cheng, Di;Xu, Ji-Fiao;Yu, Tao
背景：肠道屏障功能障碍与2型糖尿病患者的菌群失调和慢性肠道炎症有关。尽管越来越多的证据表明，慢性肠道炎症反应是由核苷酸结合寡聚化结构域样受体（NLRs）刺激的，但NLRC3与结肠上皮屏障之间的关系和确切机制在很大程度上仍然是未知的。方法：研究NLRC3在糖尿病小鼠结肠组织及结肠上皮细胞系中的作用及机制。通过上皮电阻测量、透射电镜、RNA干扰和western blotting分析了NLRC3、丁酸盐和紧密连接之间的调控机制。结果：在本研究中，我们发现NLRC3在糖尿病小鼠结肠组织中表达降低。NLRC3过表达改善了结肠上皮细胞屏障的完整性，上调了结肠上皮细胞的紧密连接蛋白。敲低TRAF6可减少nlrc3诱导的ZO-1/occludin表达。此外，我们证明丁酸盐可以刺激NLRC3在糖尿病小鼠和结肠上皮细胞中的表达。结肠上皮细胞上的GPR43参与丁酸盐诱导的NLRC3的激活。结论：我们的研究结果表明，NLCR3能够以traf6依赖的方式改善糖尿病患者结肠上皮屏障的完整性，并且丁酸盐通过结合GPR43在结肠上皮细胞上刺激NLCR3。
Background: Intestinal barrier dysfunctions are related to dysbacteriosis and chronic gut inflammation in type 2 diabetes. Although there is emerging evidence that the chronic gut inflammatory response is stimulated by nucleotide-binding oligomerization domain-like receptors (NLRs), the relationship and precise mechanism between NLRC3 and the colonic epithelial barrier remains largely elusive.Methods: We investigated the function and mechanism of NLRC3 in the colonic tissues of diabetic mice and colonic epithelial cell lines. The regulatory mechanism between NLRC3, butyrate and tight junctions was elucidated via a transepithelial electrical resistance measurement, transmission electron microscopy, RNA interference and western blotting.Results: In this study, we found that NLRC3 expression was decreased in the colonic tissues of diabetic mice. NLRC3 over-expression ameliorated colonic epithelial barrier integrity and up-regulated tight junction proteins in colonic epithelial cells. Knockdown of TRAF6 diminished NLRC3-induced ZO-1/occludin expression. In addition, we demonstrated that butyrate could stimulate NLRC3 expression in both diabetic mice and colonic epithelial cells. GPR43 on colonic epithelial cells is involved in the activation of NLRC3 induced by butyrate.Conclusion: Our findings demonstrated that NLCR3 could ameliorate colonic epithelial barrier integrity in diabetes mellitus in a TRAF6-dependent manner, and NLCR3 was stimulated by butyrate via binding GPR43 on colonic epithelial cells.