FGF-18 Protects the Injured Spinal cord in mice by Suppressing Pyroptosis and Promoting Autophagy via the AKT-mTOR-TRPML1 axis

doi:10.1007/s12035-023-03503-8

科研成果详情

题名	FGF-18 Protects the Injured Spinal cord in mice by Suppressing Pyroptosis and Promoting Autophagy via the AKT-mTOR-TRPML1 axis
作者	Li, Feida1,2,3; Cai, Tingwen1,2,3; Yu, Letian 4; Yu, Gaoxiang1,2,3; Zhang, Haojie 1,2,3; Geng, Yibo1,2,3; Kuang, Jiaxuan1,2,3,5; Wang, Yongli 2,3,6; Cai, Yuepiao7; Xiao, Jian7; Wang, Xiangyang1,2,3; Ding, Jian1,2,3; Xu, Hui1,2,3; Ni, Wenfei1,2,3; Zhou, Kailiang 1,2,3,5
发表日期	2023-08-15
发表期刊	MOLECULAR NEUROBIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	FGF-18 Spinal cord injury Autophagy Pyroptosis AKT-mTOR-TRPML1 axis
其他关键词	GROWTH-FACTOR 18 ; AUGMENTING AUTOPHAGY ; TRAUMATIC BRAIN ; ACTIVATION ; FGF18 ; INFLAMMATION ; NECROPTOSIS ; PATHWAYS ; STRESS ; DAMAGE
摘要	Spinal cord injury (SCI) is a severe medical condition with lasting effects. The efficacy of numerous clinical treatments is hampered by the intricate pathophysiological mechanism of SCI. Fibroblast growth factor 18 (FGF-18) has been found to exert neuroprotective effects after brain ischaemia, but its effect after SCI has not been well explored. The aim of the present study was to explore the therapeutic effect of FGF-18 on SCI and the related mechanism. In the present study, a mouse model of SCI was used, and the results showed that FGF-18 may significantly affect functional recovery. The present findings demonstrated that FGF-18 directly promoted functional recovery by increasing autophagy and decreasing pyroptosis. In addition, FGF-18 increased autophagy, and the well-known autophagy inhibitor 3-methyladenine (3MA) reversed the therapeutic benefits of FGF-18 after SCI, suggesting that autophagy mediates the therapeutic effects of FGF-18 on SCI. A mechanistic study revealed that after stimulation of the protein kinase B (AKT)-transient receptor potential mucolipin 1 (TRPML1)-calcineurin signalling pathway, the FGF-18-induced increase in autophagy was mediated by the dephosphorylation and nuclear translocation of transcription factor E3 (TFE3). Together, these findings indicated that FGF-18 is a robust autophagy modulator capable of accelerating functional recovery after SCI, suggesting that it may be a promising treatment for SCI in the clinic.
资助项目	National Natural Science Foundation of China[No. 82072192];Public Welfare Application Technology Research Project of Zhejiang Province[No. LGF20H150003];Wenzhou Science and Technology Bureau Foundation[No. Y20210438];Zhejiang Traditional Chinese Medicine Administration[No. 2021ZB183]
出版者	SPRINGER
ISSN	0893-7648
EISSN	1559-1182
卷号	61 期号:1 页码:55-73
DOI	10.1007/s12035-023-03503-8
页数	19
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:001048065800002
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	37581847
SCOPUSEID	2-s2.0-85167908091
通讯作者地址	[Ding, Jian]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,325027,China ; [Xu, Hui]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,325027,China ; [Ni, Wenfei]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,325027,China ; [Zhou, Kailiang]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,325027,China
Scopus学科分类	Neuroscience (miscellaneous);Neurology;Cellular and Molecular Neuroscience
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/182326
专题	药学院（分析测试中心）第二临床医学院、附属第二医院、育英儿童医院仁济学院研究生工作部（研究生院）其他_温州医科大学慈溪生物医药研究院
通讯作者	Ding, Jian; Xu, Hui; Ni, Wenfei; Zhou, Kailiang
作者单位	1.Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,325027,China; 2.Zhejiang Provincial Key Laboratory of Orthopaedics,Wenzhou,325027,China; 3.The Second Clinical Medical College of Wenzhou Medical University,Wenzhou,325027,China; 4.Renji College of Wenzhou Medical University,Wenzhou,325027,China; 5.Cixi Biomedical Research Institute,Wenzhou Medical University,Ningbo,315300,China; 6.Department of Orthopaedics,Huzhou Basic and Clinical Translation of Orthopaedics key Laboratory,Huzhou Central Hospital,Huzhou,313300,China; 7.School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	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
通讯作者单位	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
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Li, Feida,Cai, Tingwen,Yu, Letian,et al. FGF-18 Protects the Injured Spinal cord in mice by Suppressing Pyroptosis and Promoting Autophagy via the AKT-mTOR-TRPML1 axis[J]. MOLECULAR NEUROBIOLOGY,2023,61(1):55-73.
APA	Li, Feida., Cai, Tingwen., Yu, Letian., Yu, Gaoxiang., Zhang, Haojie., ... & Zhou, Kailiang. (2023). FGF-18 Protects the Injured Spinal cord in mice by Suppressing Pyroptosis and Promoting Autophagy via the AKT-mTOR-TRPML1 axis. MOLECULAR NEUROBIOLOGY, 61(1), 55-73.
MLA	Li, Feida,et al."FGF-18 Protects the Injured Spinal cord in mice by Suppressing Pyroptosis and Promoting Autophagy via the AKT-mTOR-TRPML1 axis".MOLECULAR NEUROBIOLOGY 61.1(2023):55-73.