Department of Spleen-stomach Hepatobiliary, Lianyungang Hospital of Traditional Chinese Medicine, Jiangsu Province, China.
Department of Digestive Internal Medicine, Lianyungang Second People's Hospital, Jiangsu Province, China.
Kaohsiung J Med Sci. 2021 Jun;37(6):497-504. doi: 10.1002/kjm2.12359. Epub 2021 Jan 28.
Ulcerative colitis (UC) is a chronic multifactorial inflammatory bowel disease that severely impairs patients' life quality. microRNAs (miRNAs) have been reported to exhibit potential therapeutic effects in the management of UC. With the aim to investigate the regulatory effects of miR-330 on UC-related colon tissue damage and inflammation, a rat model of experimental colitis was established by oral administration of dextran sodium sulfate (DSS). DSS-treated rats showed mucosal damage, colonic inflammation, and elevated myeloperoxidase activity compared with the healthy controls. Dual-luciferase reporter assay confirmed the binding of interleukin-1 receptor-associated kinase 1 (IRAK1) and miR-330. Subsequently, rats were intracolonically injected with miR-330 argomir with/without administration of IRAK1 during DSS treatment. The miR-330 overexpression reduced DSS-induced colonic injury and the production of proinflammatory cytokines. The level of IRAK1 was negatively regulated by the expression of miR-330. IRAK1 overexpression abolished the protective effect of miR-330 on DSS-induced colonic inflammation and mucosal injury in rats. In conclusion, we clarify the role of miR-330 in pathogenesis of UC, suggesting miR-330 alleviated DSS-induced colitis by downregulating IRAK1, shedding lights on miR-330 as a therapeutic candidate for UC treatment.
溃疡性结肠炎（UC）是一种慢性多因素炎症性肠病，严重影响患者的生活质量。研究表明，microRNAs（miRNAs）在溃疡性结肠炎的治疗中具有潜在的治疗作用。本研究旨在探讨 miR-330 对 UC 相关结肠组织损伤和炎症的调控作用，通过给予葡聚糖硫酸钠（DSS）建立实验性结肠炎大鼠模型。与健康对照组相比，DSS 处理的大鼠表现出黏膜损伤、结肠炎症和髓过氧化物酶活性升高。双荧光素酶报告基因实验证实了白细胞介素-1 受体相关激酶 1（IRAK1）与 miR-330 的结合。随后，在 DSS 处理期间，通过结肠内注射 miR-330 反义寡核苷酸（antagomir）和/或 IRAK1 对大鼠进行处理。miR-330 的过表达减轻了 DSS 诱导的结肠损伤和促炎细胞因子的产生。miR-330 的表达负调控 IRAK1 的水平。IRAK1 的过表达消除了 miR-330 对 DSS 诱导的大鼠结肠炎症和黏膜损伤的保护作用。综上所述，本研究阐明了 miR-330 在 UC 发病机制中的作用，提示 miR-330 通过下调 IRAK1 减轻 DSS 诱导的结肠炎，为 miR-330 作为 UC 治疗的候选药物提供了依据。
