TY - JOUR
T1 - Eph/ephrin signalling serves a bidirectional role in lipopolysaccharide-induced intestinal injury
AU - Xiong, Ying
AU - Li, Kai Xue
AU - Wei, Hong
AU - Jiao, Lu
AU - Yu, Shao Yong
AU - Zeng, Li
N1 - Funding Information:
The present study was supported by the International Scientific and Technological Cooperation Projects of Shenzhen Collaborative Innovation Technology Plan (grant no. GJHZ20150316141713255).
Publisher Copyright:
© 2018 Spandidos Publications. All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
KW - Ephrin
KW - Erythropoietin-producing hepatocellular receptor
KW - Lipopolysaccharide
KW - Post-infectious irritable bowel syndrome
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U2 - 10.3892/mmr.2018.9169
DO - 10.3892/mmr.2018.9169
M3 - Article
C2 - 29901151
AN - SCOPUS:85049573852
SN - 1791-2997
VL - 18
SP - 2171
EP - 2181
JO - Molecular Medicine Reports
JF - Molecular Medicine Reports
IS - 2
ER -