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

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

Research output: Contribution to journalArticle

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 1 2018

Fingerprint

Ephrins
Ephrin-B3
Erythropoietin
Lipopolysaccharides
Ephrin-A1
Wounds and Injuries
Irritable Bowel Syndrome
Monoclonal Antibodies
Catenins
Intestinal Diseases
Proto-Oncogene Proteins c-akt
Wnt Signaling Pathway
Vascular Cell Adhesion Molecule-1
Chemokine CCL2
Intercellular Adhesion Molecule-1
Interleukin-1
Neuroglia
Interleukin-6
Colon
Up-Regulation

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

Cite this

Eph/ephrin signalling serves a bidirectional role in lipopolysaccharide-induced intestinal injury. / Xiong, Ying; Li, Kai Xue; Wei, Hong; Jiao, Lu; Yu, Shaoyong; Zeng, Li.

In: Molecular Medicine Reports, Vol. 18, No. 2, 01.08.2018, p. 2171-2181.

Research output: Contribution to journalArticle

Xiong, Ying ; Li, Kai Xue ; Wei, Hong ; Jiao, Lu ; Yu, Shaoyong ; Zeng, Li. / Eph/ephrin signalling serves a bidirectional role in lipopolysaccharide-induced intestinal injury. In: Molecular Medicine Reports. 2018 ; Vol. 18, No. 2. pp. 2171-2181.
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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)-1{\ss}, 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.",
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