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埃布B3结合蛋白1(EBP1)通过介导Akt信号通路参与肠道炎症的调节。

ErbB3 binding protein 1 (EBP1) participates in the regulation of intestinal inflammation via mediating Akt signaling pathway.

作者信息

Miao Xianjing, Tang Qiyun, Miao Xiaobing, Wu Yaxun, Qian Ji, Zhao Weijuan, Wang Liang, Li Liren, Zhang Dongmei

机构信息

Department of Gastroenterology, Affiliated Hospital of Nantong University; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China.

Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210000, Jiangsu Province, People's Republic of China.

出版信息

Mol Immunol. 2015 Oct;67(2 Pt B):540-51. doi: 10.1016/j.molimm.2015.07.032.

Abstract

ErbB3 binding protein-1 (EBP1) belongs to a family of DNA/RNA binding proteins implicated in cell growth, differentiation and apoptosis. Previous data demonstrated that EBP1 regulates phosphorylation of Akt to drive tumor progress. However, the expression and biological functions of EBP1 in ulcerative colitis (UC) remain unclear. In this study, we reported for the first time that EBP1 was down-regulated in intestinal epithelial cell (IECs) of patients with UC. In DSS-induced colitis, we observed the down-regulation of EBP1 accompanied with the elevated levels of proinflammatory cytokines (IL-1β, IL-6 and IL-8) and Akt activation indicators (phosphorylated Akt) in colitis IECs, indicating the possible involvement of EBP1 in regulation of intestinal inflammation via mediating Akt in UC. Employing the TNF-α-treated HT-29 cells as an IEC inflammatory model, we confirmed the negative correlation of EBP1 with Akt activation and Akt-dependent inflammation progress in vitro. EBP1 knocking down and over-expression significantly regulated TNF-α-induced Akt activation and proinflammatory cytokines expression in HT-29 cells. Taken together, our data suggested that EBP1 participates in the regulation of intestinal inflammation via mediating Akt signaling pathway.

摘要

埃布B3结合蛋白-1(EBP1)属于一类与细胞生长、分化和凋亡相关的DNA/RNA结合蛋白家族。先前的数据表明,EBP1调节Akt的磷酸化以推动肿瘤进展。然而,EBP1在溃疡性结肠炎(UC)中的表达及生物学功能仍不清楚。在本研究中,我们首次报道EBP1在UC患者的肠上皮细胞(IECs)中表达下调。在葡聚糖硫酸钠(DSS)诱导的结肠炎中,我们观察到EBP1下调,同时结肠炎IECs中促炎细胞因子(IL-1β、IL-6和IL-8)水平升高以及Akt激活指标(磷酸化Akt)升高,这表明EBP1可能通过在UC中介导Akt参与肠道炎症的调节。利用经肿瘤坏死因子-α(TNF-α)处理的HT-29细胞作为IEC炎症模型,我们在体外证实了EBP1与Akt激活及Akt依赖性炎症进展呈负相关。EBP1敲低和过表达显著调节了TNF-α诱导的HT-29细胞中Akt激活和促炎细胞因子表达。综上所述,我们的数据表明EBP1通过介导Akt信号通路参与肠道炎症的调节。

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