Qian Xiao-Xian, Cai Chen-Wen, Li Han-Yang, Lai Li-Jie, Song Dong-Juan, Qiao Yu-Qi, Shen Jun, Ran Zhi-Hua
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, Shanghai, Shanghai, China.
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, Shanghai, Shanghai, China.
Therap Adv Gastroenterol. 2019 Oct 16;12:1756284819880733. doi: 10.1177/1756284819880733. eCollection 2019.
Transcribed ultraconserved region (T-UCR) uc.261 is reported to participate in intestinal mucosa barrier damage in Crohn's disease (CD). The aim of this study was to determine the association with disease activity and intestinal permeability.
Uc.261 level in colon mucosa and Harvey-Bradshaw Index (HBI) were evaluated in 20 active CD patients. Uc.261 expression and transepithelial electrical resistance (TEER) were determined in Caco2 and T84 cells treated with tumor necrosis factor alpha (TNF-α), respectively. Body weight, disease activity index (DAI), colon length, histological index (HI), intestinal permeability to FITC-dextran, uc.261, and tight junction proteins (TJPs) levels were evaluated in BALB/C mice treated with saline enema, trinitrobenzene sulfonic acid (TNBS)/ethanol enema, and anti-TNF-α monoclonal antibody injection, respectively.
Uc.261 expression was overexpressed in CD patients, TNF-α treated cells, and colitis mice. Uc.261 expression was positively correlated with HBI ( = 0.582, = 0.007) in CD patients, and positively correlated with TNF-α concentration and negatively correlated TEER in Caco2 and T84 cells (all < 0.05). Furthermore, uc.261 was positively correlated with DAI ( = 0.824, = 0.008), HI ( = 0.672, = 0.021), and intestinal permeability ( = 0.636, = 0.012), while negatively correlated with body weight ( = -0.574, = 0.035), colon length ( = -0.866, = 0.017), and TJP expression (all < 0.05) in colitis mice.
Uc.261 expression was closely correlated with disease activity and intestinal permeability in CD. Anti-TNF-α treatment may play its role through suppressing uc.261 expression in colitis mice.
据报道,转录超保守区域(T-UCR)uc.261参与克罗恩病(CD)的肠黏膜屏障损伤。本研究旨在确定其与疾病活动度及肠道通透性的关联。
对20例活动期CD患者评估结肠黏膜中uc.261水平及哈维-布拉德肖指数(HBI)。分别测定用肿瘤坏死因子α(TNF-α)处理的Caco2细胞和T84细胞中的uc.261表达及跨上皮电阻(TEER)。分别评估用生理盐水灌肠、三硝基苯磺酸(TNBS)/乙醇灌肠及注射抗TNF-α单克隆抗体处理的BALB/C小鼠的体重、疾病活动指数(DAI)、结肠长度、组织学指数(HI)、对异硫氰酸荧光素标记葡聚糖的肠道通透性、uc.261及紧密连接蛋白(TJPs)水平。
uc.261在CD患者、TNF-α处理的细胞及结肠炎小鼠中表达上调。在CD患者中,uc.261表达与HBI呈正相关(r = 0.582,P = 0.007);在Caco2细胞和T84细胞中,uc.261表达与TNF-α浓度呈正相关,与TEER呈负相关(均P < 0.05)。此外,在结肠炎小鼠中,uc.261与DAI呈正相关(r = 0.824,P = 0.008)、与HI呈正相关(r = 0.672,P = 0.021)、与肠道通透性呈正相关(r = 0.636,P = 0.012),而与体重呈负相关(r = -0.574,P = 0.035)、与结肠长度呈负相关(r = -0.866,P = 0.017)、与TJP表达呈负相关(均P < 0.05)。
uc.261表达与CD的疾病活动度及肠道通透性密切相关。抗TNF-α治疗可能通过抑制结肠炎小鼠中uc.261的表达发挥作用。