MicroRNA‐1224‐5p Aggravates Sepsis‐Related Acute Lung Injury in Mice

作者：Bing Liu, Feng Chen, Nitao Cheng, Zheng Tang, Xianguo Wang, Ming Xu · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2022 · DOI：10.1155/2022/9493710 · 被引用次数：11 · 研究领域：MicroRNA in disease regulation、Immune cells in cancer、Cancer-related molecular mechanisms research

Oxidative stress and inflammation are implicated in the development of sepsis‐related acute lung injury (ALI). MicroRNA‐1224‐5p (miR‐1224‐5p) plays critical roles in regulating inflammatory response and reactive oxygen species (ROS) production. The present study is aimed at investigating the role and underlying mechanisms of miR‐1224‐5p in sepsis‐related ALI. Mice were intratracheally injected with lipopolysaccharide (LPS, 5 mg/kg) for 12 h to induce sepsis‐related ALI. To manipulate miR‐1224‐5p level, mice were intravenously injected with the agomir, antagomir, or matched controls for 3 consecutive days. Murine peritoneal macrophages were stimulated with LPS (100 ng/mL) for 6 h to further validate the role of miR‐1224‐5p in vitro . To inhibit adenosine 5 ′ ‐monophosphate‐activated protein kinase alpha (AMPK α ) or peroxisome proliferator activated receptor‐gamma (PPAR‐ γ ), compound C or GW9662 was used in vivo and in vitro . We found that miR‐1224‐5p levels in lungs were elevated by LPS injection, and that the miR‐1224‐5p antagomir significantly alleviated LPS‐induced inflammation, oxidative stress, and ALI in mice. Conversely, the miR‐1224‐5p agomir aggravated inflammatory response, ROS generation, and pulmonary dysfunction in LPS‐treated mice. In addition, the miR‐1224‐5p antagomir reduced, while the miR‐1224‐5p agomir aggravated LPS‐induced inflammation and oxidative stress in murine peritoneal macrophages. Further findings revealed that miR‐1224‐5p is directly bound to ...