Lin Qiuling, Zhang Dingguo, Zhang Jian, Luo Weixiang, Xu Zhenglei, Yao Jun, Wang Lisheng
Department of General Practice, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
Front Pharmacol. 2022 Sep 14;13:991448. doi: 10.3389/fphar.2022.991448. eCollection 2022.
The incidence of ulcerative colitis (UC) in China has significantly increased over the past 10 years. Here we aim to explore potential diagnostic biomarkers and anti-inflammatory targets associated with UC. Patients with UC were enrolled in this study. The expression of lncRNAs and mRNAs in the nidus of the gut mucosa and adjacent normal mucosa samples was evaluated by RNA sequencing. The role of DLEU2 in inflammation and NF-κB signaling pathway was examined by RT-qPCR, Western blotting, and ELISA with human macrophage-like cells derived from THP-1. 564 lncRNAs and 859 mRNAs are significantly altered in the nidus of the gut mucosa of UC patients. Among the differentially expressed lncRNAs, DLEU2 changes the most. The expression of DLEU2 is negatively associated with inflammatory factors such as , , , , and . Mechanistically, DLEU2 exerts anti-inflammatory activity by inhibiting the NF-κB signaling pathway. In conclusion, the lncRNA DLEU2 in the intestinal mucosa is dysregulated upon gut inflammation and may act as a diagnostic biomarker and a therapeutic target for UC.
在过去10年中,中国溃疡性结肠炎(UC)的发病率显著上升。在此,我们旨在探索与UC相关的潜在诊断生物标志物和抗炎靶点。本研究纳入了UC患者。通过RNA测序评估肠道黏膜病灶及相邻正常黏膜样本中lncRNAs和mRNAs的表达。利用源自THP-1的人巨噬细胞样细胞,通过RT-qPCR、蛋白质免疫印迹法和酶联免疫吸附测定法检测DLEU2在炎症和NF-κB信号通路中的作用。564种lncRNAs和859种mRNAs在UC患者肠道黏膜病灶中显著改变。在差异表达的lncRNAs中,DLEU2变化最为明显。DLEU2的表达与白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α、白细胞介素-8和单核细胞趋化蛋白-1等炎症因子呈负相关。从机制上讲,DLEU2通过抑制NF-κB信号通路发挥抗炎活性。总之,肠道炎症时肠黏膜中的lncRNA DLEU2表达失调,可能作为UC的诊断生物标志物和治疗靶点。