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

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

doi:10.3892/mmr.2018.9169

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

Authors:
- Ying Xiong
- Kai‑Xue Li
- Hong Wei
- Lu Jiao
- Shao‑Yong Yu
- Li Zeng
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Affiliations: Department of Gastroenterology, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, P.R. China, Department of Gastroenterology, The Second People's Hospital of Shenzhen, Shenzhen, Guangdong 518035, P.R. China, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21205‑2195, USA
Published online on: June 14, 2018 https://doi.org/10.3892/mmr.2018.9169
Pages: 2171-2181
Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 intestinal injury was evaluated in vivo and in vitro. LPS treatment significantly increased the levels of proinflammatory mediators [monocyte chemoattractant protein‑1, tumour necrosis factor α, interleukin (IL)‑1β, IL‑6, intercellular adhesion molecule 1 and vascular cell adhesion molecule‑1], activated the EphA2‑Ephrin A1, protein kinase B (Akt)‑nuclear factor (NF)‑κB, Src‑NF‑κB and Wnt/β‑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‑κB, Src‑NF‑κB and Wnt/β‑catenin signalling pathways. In addition, 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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