MiR-29a-3p Improves Acute Lung Injury by Reducing Alveolar Epithelial Cell PANoptosis

• DOI: 10.14336/ad.2021.1023
• Publication Date: 2022-05-20T00:36:12Z
• Authors: Yanhui Cui; Xueqin Wang; Fengyu Lin; Wen Li; Yuhao Zhao; Fei Zhu; Hang Yang; Mingjun Rao; Yi li; Huaying Liang; Minhui Dai; Ben Liu; Lingli Chen; Duoduo Han; Rongli Lu; Wenzhong Peng; Yan Zhang; Chao Song; Yanwei Luo; Pinhua Pan
• Keywords: Diffuse alveolar damage

Alveolar epithelial cell damage is an important determinant of the severity acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, molecular mechanisms alveolar death during development ALI/ARDS remain unclear. In this study, we explore role miR-29a-3p in and its mechanism. Plasma samples were collected from healthy controls ARDS patients. Mice intratracheally instilled with lipopolysaccharide (LPS) to establish injury. N6-adenosine (m6A) quantification, RNA-binding protein immunoprecipitation, viability assay, quantitative real-time polymerase chain reaction, western blotting performed. We found that was down-regulated plasma patients tissue ALI model mice, agomir injection levels inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) lungs, reducing PANoptosis as evaluated by downregulation Z-DNA binding 1 (ZBP1), gasdermin D (GSDMD), caspase-3, caspase-8, mixed lineage kinase domain-like (MLKL), ultimately improving injury mice. Mechanism studies demonstrated knockout methyltransferase 3 (N6-adenosine-methyltransferase complex catalytic subunit) removed m6A modification reduced expression. Our findings suggest a potential target can be manipulated for ALI/ARDS.