Regulation of Autophagy and Ubiquitinated Protein Accumulation by bFGF Promotes Functional Recovery and Neural Protection in a Rat Model of Spinal Cord Injury

doi:10.1007/s12035-013-8432-8

科研成果详情

题名	Regulation of Autophagy and Ubiquitinated Protein Accumulation by bFGF Promotes Functional Recovery and Neural Protection in a Rat Model of Spinal Cord Injury
作者	Zhang, Hong-Yu1; Wang, Zhou-Guang 1,2; Wu, Fen-Zan1; Kong, Xiao-Xia3; Yang, Jie 1; Lin, Bei-Bei1; Zhu, Shi-Ping 4; Lin, Li1; Gan, Chao-Shi 2; Fu, Xiao-Bing 5; Li, Xiao-Kun1; Xu, Hua-Zi4; Xiao, Jian1
发表日期	2013-12
发表期刊	MOLECULAR NEUROBIOLOGY 影响因子和分区
语种	英语
原始文献类型	Review
关键词	Autophagy bFGF PI3K/Akt/mTOR Ubiquitin p62 Spinal cord injury
其他关键词	FIBROBLAST-GROWTH-FACTOR ; ENDOPLASMIC-RETICULUM STRESS ; CELL-DEATH ; NEUROTROPHIC FACTOR ; INDUCED APOPTOSIS ; RAPAMYCIN ; NEUROPROTECTION ; INHIBITION ; DISEASES ; PATHWAY
摘要	The role of autophagy in the recovery of spinal cord injury remains controversial; in particular, the mechanism of autophagy regulated degradation of ubiquitinated proteins has not been discussed to date. In this study, we investigated the protective role of basic fibroblast growth factor (bFGF) both in vivo and in vitro and demonstrated that excessive autophagy and ubiquitinated protein accumulation is involved in the rat model of trauma. bFGF administration improved recovery and increased the survival of neurons in spinal cord lesions in the rat model. The protective effect of bFGF is related to the inhibition of autophagic protein LC3II levels; bFGF treatment also enhances clearance of ubiquitinated proteins by p62, which also increases the survival of neuronal PC-12 cells. The activation of the downstream signals of the PI3K/Akt/mTOR pathway by bFGF treatment was detected both in vivo and in vitro. Combination therapy including the autophagy activator rapamycin partially abolished the protective effect of bFGF. The present study illustrates that the role of bFGF in SCI recovery is related to the inhibition of excessive autophagy and enhancement of ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling. Overall, our study suggests a new trend for bFGF drug development for central nervous system injuries and sheds light on protein signaling involved in bFGF action.
资助项目	Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents; National Natural Science Funding of ChinaNational Natural Science Foundation of China (NSFC) [81200958, 81200010]; State Key Basic Research Development Program [2012CB518105]; Zhejiang Provincial Project of Key Group [2010R5004202]; Ninbo Natural Science Foundation [2012A610255]
出版者	HUMANA PRESS INC
出版地	TOTOWA
ISSN	0893-7648
EISSN	1559-1182
卷号	48 期号:3 页码:452-464
DOI	10.1007/s12035-013-8432-8
页数	13
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:000326714700006
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	23516099
SCOPUSEID	2-s2.0-84887992069
通讯作者地址	[Xiao, Jian]Wenzhou Med Coll, Sch Pharm, Key Lab Biotechnol & Pharmaceut Engn, Wenzhou 325035, Peoples R China.
引用统计	被引频次：120[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/1868
专题	药学院（分析测试中心）附属第二医院第二临床医学院、附属第二医院、育英儿童医院研究生工作部（研究生院）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.Wenzhou Med Coll, Sch Pharm, Key Lab Biotechnol & Pharmaceut Engn, Wenzhou 325035, Peoples R China; 2.Wenzhou Med Coll, Cixi Hosp, Dept Neurol, Ningbo 315300, Zhejiang, Peoples R China; 3.Wenzhou Med Coll, Basic Med Sch, Teaching Ctr Funct Expt, Inst Hypoxia Med Res, Wenzhou 325035, Peoples R China; 4.Wenzhou Med Coll, Affiliated Hosp 2, Dept Orthopaed, Wenzhou 325000, Peoples R China; 5.Chinese Peoples Liberat Army Gen Hosp, Inst Basic Med Sci, Beijing 100853, Peoples R China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Zhang, Hong-Yu,Wang, Zhou-Guang,Wu, Fen-Zan,et al. Regulation of Autophagy and Ubiquitinated Protein Accumulation by bFGF Promotes Functional Recovery and Neural Protection in a Rat Model of Spinal Cord Injury[J]. MOLECULAR NEUROBIOLOGY,2013,48(3):452-464.
APA	Zhang, Hong-Yu., Wang, Zhou-Guang., Wu, Fen-Zan., Kong, Xiao-Xia., Yang, Jie., ... & Xiao, Jian. (2013). Regulation of Autophagy and Ubiquitinated Protein Accumulation by bFGF Promotes Functional Recovery and Neural Protection in a Rat Model of Spinal Cord Injury. MOLECULAR NEUROBIOLOGY, 48(3), 452-464.
MLA	Zhang, Hong-Yu,et al."Regulation of Autophagy and Ubiquitinated Protein Accumulation by bFGF Promotes Functional Recovery and Neural Protection in a Rat Model of Spinal Cord Injury".MOLECULAR NEUROBIOLOGY 48.3(2013):452-464.