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抑制 miR-155 可减少实验性胰腺炎模型中的自噬损伤并改善预后。

Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model.

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, P. R. China.

Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.

出版信息

Cell Death Dis. 2019 Apr 3;10(4):303. doi: 10.1038/s41419-019-1545-x.

Abstract

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.

摘要

急性胰腺炎(AP)是一种常见的消化系统疾病,其特征为胰腺炎症。miR-155 在促进炎症和抑制抗炎途径的激活方面发挥作用。自噬受损可能会促进酶原激活、异常的腺泡细胞分泌、细胞死亡和炎症反应,从而加重 AP。本研究旨在通过体内炎症和自噬受损来确定沉默 miR-155 对 AP 的影响。在这项研究中,通过尾静脉注射 AAV(腺相关病毒)介导的 miR-155 和 miR-155 海绵来注射小鼠。3 周后,通过腹腔内(IP)注射 cerulein 诱导 AP。在 24 小时后分析胰腺和肺组织。沉默 miR-155 通过阻止不能与溶酶体融合的自噬体的积累,通过靶向 TAB2 减少胰腺炎症,从而改善三种小鼠 AP 模型中的胰腺和肺损伤。3-MA 可减少异常自噬体的积累,从而减轻因 miR-155 水平升高而加重的胰腺损伤。这些发现表明抑制 miR-155 有望限制胰腺炎的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a234/6447551/1e2141bb74bc/41419_2019_1545_Fig1_HTML.jpg

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