Delivery of miR-26a-5p by Subcutaneous Adipose Tissue-Derived Extracellular Vesicles Alleviates Acute Lung Injury in Mice Through CHUK/NF-κB Pathway

作者：Yu Xie, Liuyi Ran, C. X. Yue, Chenxing Wang, Fengming Chen, Ying Hua Su, Qin Yin, Qiuhong Zhang, Jie Liu, Ning Du, Li Zhang, Yu Jiang, Gang Liu · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s514623 · 被引用次数：7 · 研究领域：Extracellular vesicles in disease、Cardiovascular Disease and Adiposity、Adipokines, Inflammation, and Metabolic Diseases

Background: Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung injury and high mortality rates due to severe inflammation. Adipose tissue, functioning as both an endocrine and immune organ, plays a crucial role in immune regulation by secreting a variety of adipokines. Among these, adipose tissue-derived extracellular vesicles (EVs) have emerged as novel mediators of intercellular communication, capable of delivering bioactive molecules such as microRNAs to target cells. This study aimed to elucidate the immunomodulatory roles and underlying mechanisms of adipose tissue-derived EVs in the pathogenesis of ARDS. Methods: Subcutaneous adipose tissue extracellular vesicles (SAT-EVs) were collected from the mice via ultracentrifugation. C57BL/6 mice were administered SAT-EVs (1×10^9 particles per mouse) via tail vein injection, followed by an intraperitoneal Lipopolysaccharide (LPS) injection three hours later to induce acute respiratory distress syndrome (ARDS). The mice were euthanized after 18 h to evaluate the permeability of the microvessels and level of inflammation in the lungs. For in vitro experiments, RAW 264.7 macrophages were stimulated with LPS, with or without SAT-EVs, as a control, to evaluate the inflammatory response of the macrophages. Results: SAT-EVs treatment enhanced the survival rate of ARDS mice and reduced pulmonary vascular permeability. SAT-EVs were internalized by alveolar macrophages, leading to an attenuation of inflammation, ...