Open AccessMiR-29a-3p Improves Acute Lung Injury by Reducing Alveolar Epithelial Cell PANoptosis
Author(s) -
Yanhui Cui,
Xueqin Wang,
Fengyu Lin,
Wen Li,
Yuhao Zhao,
Fei Zhu,
Hang Yang,
Mingjun Rao,
Yang Li,
Huaying Liang,
Minhui Dai,
Ben Liu,
Lingli Chen,
Duoduo Han,
Rongli Lu,
Wenzhong Peng,
Yan Zhang,
Song Chen,
Yanwei Luo,
Pinhua Pan
Publication year - 2022
Publication title -
aging and disease
Language(s) - Uncategorized
Resource type - Journals
ISSN - 2152-5250
DOI - 10.14336/ad.2021.1023
Subject(s) - ards , medicine , lipopolysaccharide , blot , lung , diffuse alveolar damage , tumor necrosis factor alpha , immunology , downregulation and upregulation , inflammation , cancer research , acute respiratory distress , biology , biochemistry , gene
Alveolar epithelial cell damage is an important determinant of the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the molecular mechanisms of alveolar epithelial death during the development of ALI/ARDS remain unclear. In this study, we explore the role of miR-29a-3p in ALI/ARDS and its molecular mechanism. Plasma samples were collected from healthy controls and ARDS patients. Mice were intratracheally instilled with lipopolysaccharide (LPS) to establish acute lung injury. N6-adenosine (m6A) quantification, RNA-binding protein immunoprecipitation, cell viability assay, quantitative real-time polymerase chain reaction, and western blotting were performed. We found that miR-29a-3p was down-regulated in plasma of ARDS patients and lung tissue of ALI model mice, and miR-29a-3p agomir injection down-regulated the levels of the inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the lungs, reducing alveolar epithelial cell PANoptosis as evaluated by the downregulation of Z-DNA binding protein 1 (ZBP1), gasdermin D (GSDMD), caspase-3, caspase-8, and mixed lineage kinase domain-like protein (MLKL), ultimately improving lung injury in the ALI model mice. Mechanism studies demonstrated that the knockout of methyltransferase 3 (N6-adenosine-methyltransferase complex catalytic subunit) removed the m6A modification of miR-29a-3p and reduced miR-29a-3p expression. Our findings suggest that miR-29a-3p is a potential target that can be manipulated for ALI/ARDS.