Wang Dongyan, Tang Maochun, Zong Pengfei, Liu Hua, Zhang Ting, Liu Yu, Zhao Yan
Department of Gastroenterology, Tenth People's Hospital of Tongji University, Shanghai, China.
The Community Health Service Center of Nanxiang Town, Shanghai, China.
Front Physiol. 2018 Jun 8;9:686. doi: 10.3389/fphys.2018.00686. eCollection 2018.
Acute pancreatitis (AP) is a serious condition associated with intestinal barrier disruption or inflammation of the pancreatic tissue. Specific microRNAs are involved in the pathogenesis of AP, during which IL-17-producing CD4 T helper (Th17) cells accumulate in the pancreas. In this study, significantly increased levels of miR-155 were detected in clinical samples from patients with AP, and overexpression of miR-155 correlated with severe AP (SAP). To identify the effect of miR-155 on T cell differentiation, we isolated CD4 T lymphocytes and experiments showed that inhibition of miR-155 significantly reversed the stress-induced increase in the Th17/Treg ratio. The results also showed that miR-155 increased the Th17-mediated inflammatory response by targeting SOCS1. The interaction between miR-155 and the 3-UTR of SOCS1 was confirmed by a dual luciferase reporter assay and RT-PCR. Experimental AP of varying severity was induced in BALB/c mice by caerulein hyperstimulation and miR-155 expression was found to increase with disease progression. Inhibition of miR-155 expression significantly improved the pathology of the pancreas. We also observed downregulation of expression of inflammatory factors, IL-17, SOCS1 and phosphorylated STAT1 after miR-155 inhibition. In summary, miR-155 regulates the Th17/Treg ratio by targeting SOCS1, most probably via direct binding to its 3-UTR region, indicating that this microRNA may be a potential biomarker and/or therapeutic target for AP.
急性胰腺炎（AP）是一种与肠屏障破坏或胰腺组织炎症相关的严重病症。特定的微小RNA参与了AP的发病机制，在此过程中，产生白细胞介素-17的CD4辅助性T细胞（Th17）在胰腺中积聚。在本研究中，在AP患者的临床样本中检测到miR-155水平显著升高，且miR-155的过表达与重症急性胰腺炎（SAP）相关。为了确定miR-155对T细胞分化的影响，我们分离了CD4 T淋巴细胞，实验表明抑制miR-155可显著逆转应激诱导的Th17/Treg比值增加。结果还表明，miR-155通过靶向细胞因子信号转导抑制因子1（SOCS1）增加Th17介导的炎症反应。通过双荧光素酶报告基因检测和逆转录-聚合酶链反应（RT-PCR）证实了miR-155与SOCS1的3'-非翻译区（3'-UTR）之间的相互作用。通过蛙皮素过度刺激在BALB/c小鼠中诱导了不同严重程度的实验性AP，发现miR-155表达随疾病进展而增加。抑制miR-155表达可显著改善胰腺病理。我们还观察到抑制miR-155后炎症因子白细胞介素-17、SOCS1和磷酸化信号转导和转录激活因子1（p-STAT1）的表达下调。总之，miR-155通过靶向SOCS1调节Th17/Treg比值，很可能是通过直接结合其3'-UTR区域实现的，这表明这种微小RNA可能是AP的潜在生物标志物和/或治疗靶点。
