Cideb Deficiency Aggravates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice by Exacerbating the Oxidative Burden in Colonic Mucosa
Cideb Deficiency Aggravates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice by Exacerbating the Oxidative Burden in Colonic Mucosa
复制标题
Cideb 缺乏会加剧结肠粘膜的氧化负担，从而加重硫酸葡聚糖钠诱发的小鼠溃疡性结肠炎
DOI：
10.1097/mib.0000000000001196
复制
发表时间：
2017
影响因子：
4.9
通讯作者：
Ye Jing
中科院分区：
文献类型：
--
作者：
Sun Chao;Zhao Yuanlin;Gao Xing;Yuan Yuan;Wang Chao;Wang Yingmei;Zhang Lijun;Gu Yu;Zhang Feng;Hu Peizhen;Wang Zhe;Li Zhuyi;Shi Jiankuan;Li Sheng;Cao Kaiyu;Ren Bingcheng;Yu Ming;Liang Weihua;Li Zengshan;Ye Jing
研究背景脂质代谢异常是溃疡性结肠炎（UC）发生发展的重要因素之一。作为脂滴相关蛋白，Cideb促进脂质从肠上皮细胞的输出，并促进肠道脂质吸收。我们发现，Cideb上调UC患者和葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的结肠粘膜，但其在UC的发病机制中的作用仍然不明确。MethodsAcute结肠炎诱导DSS在Cideb无效和野生型小鼠，炎症和氧化应激在结肠粘膜进行了评估。此外，甘油三酯的积累和氧化应激进一步分析极化Caco-2细胞过度表达的Cideb.ResultsOur目前的数据表明thasCideb-null小鼠更容易受到DSS诱导的结肠炎，和消费的高脂肪饮食加剧恶化DSS诱导的结肠炎在Cideb-null小鼠。此外，Cideb缺乏增加DSS治疗的小鼠结肠氧化应激，在高脂饮食条件下更显着。在探索其机制时，我们发现Cideb缺乏会增加DSS处理小鼠粪便和结肠粘膜中的脂质含量，尤其是那些喂食高脂饮食的小鼠。在体外的证据证明，Cideb的表达减少了甘油三酯的积累和氧化应激在极化Caco-2细胞中存在的油酸.ConclusionsOur的数据表明，Cideb起着保护作用，对UC的发展，通过减少结肠粘膜中的脂质积累和氧化损伤。因此，Cideb可能是UC的潜在治疗靶点。
BackgroundAbnormal lipid metabolism is one of many factors that contribute to the development of ulcerative colitis (UC). As a lipid droplet–associated protein, Cideb facilitated the export of lipids from enterocytes and promoted intestinal lipid absorption. We found that Cideb was upregulated in the colonic mucosa of both UC patients and dextran sodium sulfate (DSS)-induced mouse colitis, but its roles in the pathogenesis of UC are still ill-defined.MethodsAcute colitis was induced with DSS inCideb-null and wild-type mice, and the inflammation and oxidative stress were evaluated in the colonic mucosa. Moreover, triglyceride accumulation and oxidative stress were further analyzed in polarized Caco-2 cells with overexpression of Cideb.ResultsOur present data indicated thatCideb-null mice were more susceptible to DSS-induced colitis, and consumption of a high-fat diet exacerbated the deterioration of DSS-induced colitis inCideb-null mice. Moreover, Cideb deficiency increased the colonic oxidative stress in DSS-treated mice and more significant under a high-fat diet condition. In exploring the mechanism, we found that Cideb deficiency elevated the lipid content in both feces and the colonic mucosa of DSS-treated mice, especially those fed with a high-fat diet. The in vitro evidence proved that Cideb expression reduced triglyceride accumulation and oxidative stress in polarized Caco-2 cells in the presence of oleic acid.ConclusionsOur data suggest that Cideb plays a protective role against the development of UC by reducing the lipid accumulation and oxidative damage in the colonic mucosa. Therefore, Cideb could be a potential therapeutic target for UC.