Oncotarget

Research Papers:

The cross-talk between autophagy and endoplasmic reticulum stress in blood-spinal cord barrier disruption after spinal cord injury

Yulong Zhou, Yanqing Wu, Yanlong Liu, Zili He, Shuang Zou, Qingqing Wang, Jiawei Li, Zengming Zheng, Jian Chen, Fenzan Wu, Fanhua Gong, Hongyu Zhang, Huazi Xu and Jian Xiao _

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Oncotarget. 2017; 8:1688-1702. https://doi.org/10.18632/oncotarget.13777

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Abstract

Yulong Zhou1,2,*, Yanqing Wu3,*, Yanlong Liu2,*, Zili He1,2, Shuang Zou2, Qingqing Wang1,2, Jiawei Li1,2, Zengming Zheng1,2, Jian Chen1,2, Fenzan Wu4, Fanhua Gong3, Hongyu Zhang2, Huazi Xu1, Jian Xiao1,2

1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China

2Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China

3The Institute of Life Sciences, Wenzhou University, Wenzhou 325035, China

4Department of Neurosurgery, Affiliated Cixi People’s Hospital, Wenzhou Medical University, Ningbo, 315300, China

*These authors have contribute equally to this work

Correspondence to:

Jian Xiao, email: [email protected]

Huazi Xu, email: [email protected]

Keywords: spinal cord injury (SCI), blood-spinal cord barrier (BSCB), endoplasmic reticulum (ER) stress, autophagy

Received: October 05, 2016     Accepted: November 07, 2016     Published: December 02, 2016

ABSTRACT

Spinal cord injury induces the disruption of blood-spinal cord barrier and triggers a complex array of tissue responses, including endoplasmic reticulum (ER) stress and autophagy. However, the roles of ER stress and autophagy in blood-spinal cord barrier disruption have not been discussed in acute spinal cord trauma. In the present study, we respectively detected the roles of ER stress and autophagy in blood-spinal cord barrier disruption after spinal cord injury. Besides, we also detected the cross-talking between autophagy and ER stress both in vivo and in vitro. ER stress inhibitor, 4-phenylbutyric acid, and autophagy inhibitor, chloroquine, were respectively or combinedly administrated in the model of acute spinal cord injury rats. At day 1 after spinal cord injury, blood-spinal cord barrier was disrupted and activation of ER stress and autophagy were involved in the rat model of trauma. Inhibition of ER stress by treating with 4-phenylbutyric acid decreased blood-spinal cord barrier permeability, prevented the loss of tight junction (TJ) proteins and reduced autophagy activation after spinal cord injury. On the contrary, inhibition of autophagy by treating with chloroquine exacerbated blood-spinal cord barrier permeability, promoted the loss of TJ proteins and enhanced ER stress after spinal cord injury. When 4-phenylbutyric acid and chloroquine were combinedly administrated in spinal cord injury rats, chloroquine abolished the blood-spinal cord barrier protective effect of 4-phenylbutyric acid by exacerbating ER stress after spinal cord injury, indicating that the cross-talking between autophagy and ER stress may play a central role on blood-spinal cord barrier integrity in acute spinal cord injury. The present study illustrates that ER stress induced by spinal cord injury plays a detrimental role on blood-spinal cord barrier integrity, on the contrary, autophagy induced by spinal cord injury plays a furthersome role in blood-spinal cord barrier integrity in acute spinal cord injury.


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