STK11 Alleviates Pulmonary Inflammation During Acute Lung Injury by Phosphorylating AMPK to Activate Autophagy in A549 Cell Model.

PURPOSE: To investigate if protein STK11 alleviates lipopolysaccharide-induced acute lung injury (ALI), hypothesizing it activates autophagy (harmful substance clearance) via AMPK's "start signal". METHODS: Researchers used a genomics-first approach: they integrated datasets GSE66890, GSE10474, and GSE32707, screened autophagy-related differentially expressed genes in ALI via bioinformatics, and confirmed STK11 as a key regulator through protein-protein interaction analysis. They treated human lung cells with 50 μg/mL lipopolysaccharide for 24 hours to establish ALI models, then overexpressed or silenced STK11 in the cells. They assessed cell function, apoptosis, inflammatory factors, autophagy activity, and AMPK activation. RESULTS: Researchers verified STK11 as a key regulator of autophagy in ALI. STK11 overexpression significantly improved cell function, reduced apoptosis (lower pro-apoptotic/higher anti-apoptotic proteins), decreased IL-6/IL-8/TNF-α (mRNA/protein levels), enhanced autophagy (elevated LC3B-II, reduced P62, more autophagosomes), and activated AMPK. STK11 silencing reversed these protective effects and inhibited AMPK. CONCLUSION: STK11 mitigates lipopolysaccharide-induced lung cell damage by activating AMPK-mediated autophagy, emerging as a potential therapeutic target for ALI.