Gang Liu Binbin Dong Zi-Heng Ding Chao Lan Changju Zhu ^* Qi Liu ^*

• First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

In patients with acute respiratory distress syndrome, mechanical ventilation is often accompanied by ventilation-induced lung injury (VILI), which is attributed to the unphysiological lung strain (UPLS) and stress in respiratory dynamics. Platelet endothelial cell adhesion molecule-1(PECAM-1), a transmembrane protein, acts as a receptor that senses mechanical signals. The Src/STAT3 pathway plays a crucial role in the mechanotransduction network, concurrently triggering inflammatory responses.We hypothesized that the stretch caused by UPLS during mechanical ventilation can be sensed by PECAM-1 in the lungs, leading to VILI via the Src/STAT3 pathway. In this study, a VILI model was established through UPLS in rats. UPLS activated PECAM-1, Src/STAT3 signaling pathway, inflammation, and pyroptosis in our VILI model with rats, whereas inhibition of PECAM-1 or the Src/STAT3 signaling pathway decreased lung injury, inflammatory responses, and pyroptosis. Inhibition of PECAM-1 also reduced activation of the Src/STAT3 signaling pathway. The mechanism was validated through in vitro experiments with human umbilical vein endothelial cells exposed to mechanical cyclic stretch. This study suggests that UPLS contributes to VILI by activating the PECAM-1/Src/STAT3 pathway, as well as inducing inflammatory responses and pyroptosis.