Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury

Ji Young Hong, Mi Hwa Shin, Ivor S. Douglas, Kyung Soo Chung, Eun Young Kim, Ji Ye Jung, Young Ae Kang, Se Kyu Kim, Joon Chang, Young Sam Kim, Moo Suk Park

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10 Citations (Scopus)

Abstract

Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis 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 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury. Acute LPS exposure significantly up-regulated EphA2 and EphrinA1 expression. Compared with LPS + IgG mice (IgG instillation after LPS exposure), LPS + EphA2 mAb mice [EphA2 monoclonal antibody (mAb) instillation posttreatment after LPS exposure] had attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid (BALF). EphA2 mAb posttreatment down-regulated the expression of phosphoinositide 3-kinases (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 signalling 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.

Original languageEnglish
Pages (from-to)1993-2003
Number of pages11
JournalClinical Science
Volume130
Issue number21
DOIs
Publication statusPublished - 2016 Jan 1

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Hong, J. Y., Shin, M. H., Douglas, I. S., Chung, K. S., Kim, E. Y., Jung, J. Y., Kang, Y. A., Kim, S. K., Chang, J., Kim, Y. S., & Park, M. S. (2016). Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury. Clinical Science, 130(21), 1993-2003. https://doi.org/10.1042/CS20160360