Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model
Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model
复制标题
在实验性胰腺炎小鼠模型中，抑制 miR-155 可减少受损的自噬并改善预后。
DOI：
10.1038/s41419-019-1545-x
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发表时间：
2019-04-03
影响因子：
9
通讯作者：
Lu, Nonghua
中科院分区：
文献类型：
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作者：
Wan, Jianhua;Yang, Xiaoyu;Lu, Nonghua
急性胰腺炎（acute pancreatitis，AP）是一种常见的以胰腺炎症为特征的消化系统疾病. MiR-155在促进炎症和抑制抗炎途径的激活中起作用。自噬受损可促进酶原激活、腺泡细胞分泌异常、细胞死亡和炎症反应，加重AP。本研究的目的是通过其对体内炎症和自噬受损的影响来确定沉默miR-155对AP的影响。本研究通过小鼠尾静脉注射AAV（腺相关病毒）介导的miR-155和miR-155海绵。3周后，通过腹腔内（IP）注射雨蛙肽诱导AP。24小时后分析胰腺和肺组织。miR-155的沉默通过防止不能与溶酶体融合的自噬体的积累和通过靶向TAB 2减少胰腺炎症来改善三种AP小鼠模型中的胰腺和肺损伤。3-MA可减少自噬体的异常积聚，这可减轻因增加miR-155水平而加重的胰腺损伤。这些发现表明，抑制miR-155有望限制胰腺炎。
Acute pancreatitis (AP) is a common digestive disease characterized by inflammation of the pancreas. MiR-155 plays a role in promoting inflammation and inhibiting the activation of anti-inflammatory pathways. Impaired autophagy could promote zymogen activation, abnormal acinar cell secretion, cell death, and the inflammatory response to aggravate AP. The aim of this study was to ascertain the effect of silencing miR-155 on AP through its effects on inflammation and impaired autophagy in vivo. In this study, AAV(adeno-associated virus)-mediated miR-155 and miR-155 sponge were injected through the tail vein of mice. After 3 weeks, AP was induced by intraperitoneal (IP) injections of cerulein. Pancreatic and pulmonary tissues were analyzed after 24 h. Silencing of miR-155 ameliorated pancreas and lung damage in three AP models of mice by preventing accumulation of autophagosomes that are unable to fuse with lysosomes and decreasing pancreatic inflammation by targeting TAB2. 3-MA could reduce the aberrant accumulation of autophagosomes, which alleviates the pancreas damage that was aggravated by increasing miR-155 levels. These findings demonstrate that the inhibition of miR-155 holds promise for limiting pancreatitis.