C107-05 Sodium Coupled Neutral Amino Acid Transporter Snat2 as a Key Regulator of Alveolar Epithelial Cell Homeostasis in Acute Lung Injury

作者：G. Li, J. Falivene, S. Weidenfeld, L. Erfinanda, S. Schultz, W. Kuebler · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2026 · DOI：10.1093/ajrccm/aamag162.226

Acute Respiratory Distress Syndrome (ARDS) is the most frequent cause of death in intensive care units, yet effective pharmacological treatments are still lacking. Dysregulation of alveolar fluid clearance (AFC) and loss of alveolar-capillary barrier function due to alveolar epithelial cell (AEC) death are hallmarks of ARDS. The Na+-coupled neutral amino acid (AA) transporter SNAT2 belongs to the SLC38 gene family and transports one neutral AA along with one Na+. We previously demonstrated that SNAT2 is expressed in AEC and promotes AFC in isolated perfused lungs via its function as Na+ transporter. Here, we investigated the role of SNAT2 as AA transporter and its relevance in the regulation of AEC homeostasis. We hypothesized that SNAT2 might be a central regulator of AEC metabolism and fate in acute lung injury (ALI)/ARDS, and could thus represent a novel therapeutic target. In human primary AEC, SNAT2 was either inhibited by α-methylaminoisobutyric acid (MeAIB), knocked down (KD) by siRNA, or overexpressed (OE) by transfection with a SLC38A2-Myc-DDK-tagged plasmid. AEC were stimulated with a mix of LPS, IFN-γ, TNF-α and IL-1β (cytomix). After 24h, apoptosis, autophagy and ER-stress markers (ATF4, CHOP) were evaluated by qPCR, Western blot, and flow cytometry. Cell proliferation and migration were assessed by Ki67 staining, BrdU incorporation and scratch assay. Changes in cell metabolism were evaluated by Seahorse assay. In vivo, LPS (5 mg/kg BW intranasally)-induced...