Eph/ephrin signalling serves a bidirectional role in lipopolysaccharide-induced intestinal injury

Ying Xiong, Kai Xue Li, Hong Wei, Lu Jiao, Shao Yong Yu, Li Zeng

Research output: Contribution to journalArticlepeer-review

Abstract

A growing body of evidence has demonstrated that Eph/ephrin signalling may serve a central role in intestinal diseases. However, whether erythropoietin-producing hepatocellular (Eph)/ephrin signalling is associated with the development of post-infectious irritable bowel syndrome (PI-IBS) is still unknown. In the present study, the role of Eph/Ephrin signalling in lipopolysaccharide (LPS)-induced intestinalinjurywasevaluatedinvivoandinvitro.LPStreatment significantly increased the levels of proinflammatory mediators [monocyte chemoattractant protein-1, tumour necrosis factor a, interleukin (IL)-1ß, IL-6, intercellular adhesion molecule 1 and vascular cell adhesion molecule-1], activated the EphA2-Ephrin A1, protein kinase B (Akt)-nuclear factor (NF)-?B, Src-NF-?B and Wnt/ß-catenin signalling pathways, and inhibited EphB1-Ephrin B3 signalling in colon tissues, and primary cultured enteric neuronal and glial cells. Notably, EphA2 monoclonal antibody (mAb) treatment or Ephrin B3 overexpression could partially alleviate the LPS-induced upregulation of proinflammatory mediators, and Akt-NF-?B, Src-NF-?BandWnt/ß-cateninsignallingpathways.Inaddition, EphA2 mAb treatment could partially inhibit LPS-induced inactivation of EphB-Ephrin B3 signalling, while Ephrin B3 overexpression could abrogate LPS-induced activation of EphA2-Ephrin A1 signalling. EphB1/Ephrin B3 signalling may antagonise the EphA2/Ephrin A1-dependent pathway following LPS treatment. The results associated with the EphA2 signaling pathway, indicated that Eph/ephrin signalling may serve a bidirectional role in LPS-induced intestinal injury. Eph/ephrin signalling may be a novel therapeutic target for LPS-induced intestinal injury and potentially PI-IBS.

Original languageEnglish (US)
Pages (from-to)2171-2181
Number of pages11
JournalMolecular Medicine Reports
Volume18
Issue number2
DOIs
StatePublished - Aug 2018

Keywords

  • Ephrin
  • Erythropoietin-producing hepatocellular receptor
  • Lipopolysaccharide
  • Post-infectious irritable bowel syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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