Tensile Overload Injures Human Alveolar Epithelial Cells through YAP/F-Actin/MAPK Signaling

Background: Explosion shockwaves can generate overloaded mechanical forces and induce lung injuries. However, the mechanism of lung injuries caused by tensile overload is still unclear. Methods: Flow cytometry was used to detect the apoptosis of human alveolar epithelial cells (BEAS-2B) induced by tensile overload, and cell proliferation was detected using 5-ethynyl-2 & PRIME;-deoxyuridine (EdU). Immunofluorescence and Western blot analysis were used to identify the tensile overload on the actin cytoskeleton, proteins related to the mitogen-activated protein kinase (MAPK) signal pathway, and the Yes-associated protein (YAP). Results: Tensile overload reduced BEAS-2B cell proliferation and increased apoptosis. In terms of the mechanism, we found that tensile overload led to the depolymerization of the actin cytoskeleton, the activation of c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase 1/2 (ERK1/2), and the upregulation of YAP expression. Jasplakinolide (Jasp) treatment promoted the polymerization of the actin cytoskeleton and reduced the phosphorylation of tension-overload-activated JNK and ERK1/2 and the apoptosis of BEAS-2B cells. Moreover, the inhibition of the JNK and ERK1/2 signaling pathways, as well as the expression of YAP, also reduced apoptosis caused by tensile overload. Conclusion: Our study establishes the role of the YAP/F-actin/MAPK axis in tensile-induced BEAS-2B cell injury and proposes new strategies for the treatment and repair of future lung injuries.

Automated summary

This study found that tensile overload induced apoptosis and proliferation in BEAS-2B cells, activated the MAPK signaling pathway and YAP, and led to the depolymerization of the actin cytoskeleton. Treatment with jasplakinolide promoted the polymerization of the actin cytoskeleton and reduced cell apoptosis by inhibiting JNK and ERK1/2 signaling pathways and the expression of YAP. The YAP/F-actin/MAPK axis plays a role in tensile-induced cell injury and provides new strategies for the treatment and repair of lung injuries.