SPON2 suppression alleviates phosgene-induced acute lung injury in mice associated with JAK1/STAT3 signaling inhibition.

Unexpected phosgene exposure poses a significant risk for acute lung injury (ALI), a life-threatening condition associated with high mortality. The key pathological hallmarks of ALI include pulmonary inflammation, alveolar edema, and epithelial cell apoptosis. Spondin 2 (SPON2) is involved in multiple essential biological processes. However, its role in phosgene-induced ALI and the underlying mechanism are still unclear. In the present study, we observed the significant upregulation of SPON2 expression in pulmonary epithelial cells 24 h after phosgene exposure with a murine model of phosgene-induced ALI. Moreover, adeno-associated virus-mediated SPON2 knockdown attenuated inflammatory cell infiltration and alveolar collapse, reduced IL-6, enhanced IL-10 levels, and decreased apoptosis in the lungs of phosgene-exposed mice. SPON2 suppression also mitigated the inflammatory response and apoptosis in MLE-12 cells exposed to lipopolysaccharide. Furthermore, JAK1 and STAT3 phosphorylation levels were significantly increased following lipopolysaccharide stimulation and markedly reduced upon SPON2 inhibition, indicating that SPON2 is associated with the JAK1/STAT3 signaling pathway. These findings suggest that SPON2 suppression attenuates phosgene-induced ALI by regulating both the inflammatory response and apoptosis potentially involving the JAK1/STAT3 pathway. Therefore, this study suggests potential therapeutic strategies for patients with phosgene-induced ALI.