Eph-Ephrin signaling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homeostasis, and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signaling are unknown. Here, we evaluated the role of EphA2 signaling from mice with LPS-induced lung injury. Acute LPS exposure significantly upregulated EphA2 and EphrinA1 expression. Compared with LPS + IgG mice (IgG instillation after LPS exposure), LPS+ EphA2 mAb mice (EphA2 monoclonal antibody instillation posttreatment after LPS exposure) attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid. EphA2 mAb posttreatment downregulated the expression of PI3K 110γ, phospho-Akt, phospho-NF-κB p65, phospho-Src, and phospho-S6K in lung lysates. In addition, inhibiting the EphA2 receptor augmented the expression of E- cadherin, which is involved in cell-cell adhesion. Our study identified EphA2 receptor as an unrecognized modulator of several signaling pathways-including PI3K-Akt-NF-kB, Src-NF-κB, E-cadherin, and mTOR-in LPS-induced lung injury. These results suggest that EphA2 receptor inhibitors may function as novel therapeutic agents for LPS-induced lung injury.
- acute lung injury
- ©2016 The Author(s)
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