Latexin deficiency in mice up-regulates inflammation and aggravates colitis through HECTD1/Rps3/NF-κB pathway
Latexin deficiency in mice up-regulates inflammation and aggravates colitis through HECTD1/Rps3/NF-κB pathway
复制标题
小鼠乳胶素缺乏通过 HECTD1/Rps3/NF-κB 通路上调炎症并加重结肠炎
DOI：
10.1038/s41598-020-66789-x
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发表时间：
2020-06-17
影响因子：
4.6
通讯作者：
Chen, Ming
中科院分区：
文献类型：
--
作者：
Li, Yaping;Huang, Baohua;Chen, Ming
Latexin （LXN）在炎症中的作用已引起人们的关注。然而，尚无关于其在结肠炎中的作用的数据。我们报道LXN是结肠炎的抑制因子。LXN缺乏导致dss诱导小鼠结肠炎的严重程度，维甲酸对结肠炎的治疗作用需要LXN。使用蛋白质组学方法，我们证明LXN与hecd1 （E3泛素连接酶）和核糖体蛋白亚单位3 （Rps3）相互作用并形成功能复合物。IκBα是hector 1的底物之一。LXN的异位表达导致i - κ b α在肠上皮细胞中积累，而LXN的下调增强了hecd1和Rps3的相互作用，促进了i - κ b α的泛素化降解，从而增强了炎症反应。因此，我们的研究结果提供了LXN通过hector 1/Rps3/NF-κB途径调节结肠炎的新机制，并对开发以LXN为靶点治疗结肠炎的新策略具有重要意义。
The function of Latexin (LXN) in inflammation has attracted attention. However, no data are available regarding its role in colitis. We report that LXN is a suppressor of colitis. LXN deficiency leads to the severity of colitis in DSS-induced mice, and LXN is required for the therapeutic effect of retinoic acid on colitis. Using a proteomics approach, we demonstrate that LXN interacts and forms a functional complex with HECTD1 (an E3 ubiquitin ligase) and ribosomal protein subunit3 (Rps3). IκBα is one of the substrates of HECTD1. Ectopic expression of LXN leads to IκBα accumulation in intestinal epithelial cells, however, LXN knockdown enhances the interaction of HECTD1 and Rps3, contributing to the ubiquitination degradation of IκBα, and subsequently enhances inflammatory response. Thus, our findings provided a novel mechanism underlying LXN modulates colitis via HECTD1/Rps3/NF-κB pathway and significant implications for the development of novel strategies for the treatment of colitis by targeting LXN.