Retinoic Acid Induced-Autophagic Flux Inhibits ER-Stress Dependent Apoptosis and Prevents Disruption of Blood-Spinal Cord Barrier after Spinal Cord Injury

doi:10.7150/ijbs.13229

科研成果详情

题名	Retinoic Acid Induced-Autophagic Flux Inhibits ER-Stress Dependent Apoptosis and Prevents Disruption of Blood-Spinal Cord Barrier after Spinal Cord Injury
作者	Zhou, Yulong1,2; Zhang, Hongyu2; Zheng, Binbin1,2; Ye, Libing 2; Zhu, Sipin1,2; Johnson, Noah R.3; Wang, Zhouguang 2; Wei, Xiaojie4; Chen, Daqing5; Cao, Guodong 6; Fu, Xiaobing 7; Li, Xiaokun2; Xu, Hua-Zi1; Xiao, Jian 2
发表日期	2016-12-31
发表期刊	INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	blood-spinal cord barrier (BSCB) retinoic acid (RA) autophagy endocytoplasmic reticulum (ER) stress spinal cord injury (SCI)
其他关键词	ENDOPLASMIC-RETICULUM STRESS ; IMPROVES FUNCTIONAL RECOVERY ; BRAIN-BARRIER ; PROTECTS ; INFLAMMATION ; CELLS ; MODEL ; GRP78 ; RATS ; DIFFERENTIATION
摘要	Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB) which leads to infiltration of blood cells, an inflammatory response, and neuronal cell death, resulting spinal cord secondary damage. Retinoic acid (RA) has a neuroprotective effect in both ischemic brain injury and SCI, however the relationship between BSCB disruption and RA in SCI is still unclear. In this study, we demonstrated that autophagy and ER stress are involved in the protective effect of RA on the BSCB. RA attenuated BSCB permeability and decreased the loss of tight junction (TJ) molecules such as P120, beta-catenin, Occludin and Claudin5 after injury in vivo as well as in Brain Microvascular Endothelial Cells (BMECs). Moreover, RA administration improved functional recovery in the rat model of SCI. RA inhibited the expression of CHOP and caspase-12 by induction of autophagic flux. However, RA had no significant effect on protein expression of GRP78 and PDI. Furthermore, combining RA with the autophagy inhibitor chloroquine (CQ) partially abolished its protective effect on the BSCB via exacerbated ER stress and subsequent loss of tight junctions. Taken together, the neuroprotective role of RA in recovery from SCI is related to prevention of of BSCB disruption via the activation of autophagic flux and the inhibition of ER stress-induced cell apoptosis. These findings lay the groundwork for future translational studies of RA for CNS diseases, especially those related to BSCB disruption.
资助项目	National Natural Science Funding of ChinaNational Natural Science Foundation of China (NSFC) [81572237, 81372112, 81302775, 81472165]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [LY14H090013, LY14H150010, LY14H170002]; Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents; State Key Basic Research Development Program [2012CB518105]; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS079345] Funding Source: NIH RePORTER; Veterans AffairsUS Department of Veterans Affairs [I01BX002346] Funding Source: NIH RePORTER
出版者	IVYSPRING INT PUBL
出版地	LAKE HAVEN
ISSN	1449-2288
卷号	12 期号:1 页码:87-99
DOI	10.7150/ijbs.13229
页数	13
WOS类目	Biochemistry & Molecular Biology ; Biology
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS记录号	WOS:000366276800008
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	26722220
SCOPUSEID	2-s2.0-84952884477
通讯作者地址	[Xiao, Jian]School of Pharmacy,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Ecology, Evolution, Behavior and Systematics;Applied Microbiology and Biotechnology;Molecular Biology;Developmental Biology;Cell Biology
TOP期刊	TOP期刊
引用统计	被引频次：34[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/8595
专题	第二临床医学院、附属第二医院、育英儿童医院附属第二医院药学院（分析测试中心）_分子药理研究与教学中心其他_附属慈溪医院（慈溪市人民医院）
通讯作者	Xiao, Jian
作者单位	1.Department of Orthopaedics,The Second Affiliated Hospital,Wenzhou Medical University,Wenzhou,325035,China; 2.Molecular Pharmacology Research Center,School of Pharmacy,Wenzhou Medical University,Wenzhou,325035,China; 3.Department of Bioengineering and the McGowan Institute for Regenerative Medicine,University of Pittsburgh,Pittsburgh,15219,United States; 4.Department of Neurosurgery,Cixi People’s Hospital,Wenzhou Medical University,Ningbo,315300,China; 5.Department of Emergency,The Second Affiliated Hospital,Wenzhou Medical University,Wenzhou,325035,China; 6.Department of Neurology,University of Pittsburgh School of Medicine,Pittsburgh,United States; 7.Institute of Basic Medical Science,Chinese PLA General Hospital,Beijing,100853,China
第一作者单位	附属第二医院; 药学院（分析测试中心）; 分子药理研究与教学中心
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	Zhou, Yulong,Zhang, Hongyu,Zheng, Binbin,et al. Retinoic Acid Induced-Autophagic Flux Inhibits ER-Stress Dependent Apoptosis and Prevents Disruption of Blood-Spinal Cord Barrier after Spinal Cord Injury[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2016,12(1):87-99.
APA	Zhou, Yulong., Zhang, Hongyu., Zheng, Binbin., Ye, Libing., Zhu, Sipin., ... & Xiao, Jian. (2016). Retinoic Acid Induced-Autophagic Flux Inhibits ER-Stress Dependent Apoptosis and Prevents Disruption of Blood-Spinal Cord Barrier after Spinal Cord Injury. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 12(1), 87-99.
MLA	Zhou, Yulong,et al."Retinoic Acid Induced-Autophagic Flux Inhibits ER-Stress Dependent Apoptosis and Prevents Disruption of Blood-Spinal Cord Barrier after Spinal Cord Injury".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 12.1(2016):87-99.