A snake cathelicidin enhances transcription factor EB-mediated autophagy and alleviates ROS-induced pyroptosis after ischaemia-reperfusion injury of island skin flaps

doi:10.1111/bph.16268

科研成果详情

题名	A snake cathelicidin enhances transcription factor EB-mediated autophagy and alleviates ROS-induced pyroptosis after ischaemia-reperfusion injury of island skin flaps
作者	Yang, Ningning1,2,3; Yu, Gaoxiang1,2,3; Lai, Yingying1,2,3; Zhao, Jiayi 4; Chen, Zhuliu1,2,3; Chen, Liang 1,2,3; Fu, Yuedong1,2,3; Fang, Pin1,2,3; Gao, Weiyang1,2,3; Cai, Yuepiao4; Li, Zhijie 1,2,3; Xiao, Jian4; Zhou, Kailiang 1,2,3; Ding, Jian1,2,3
发表日期	2023-11-27
发表期刊	BRITISH JOURNAL OF PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access ; Journal Article
关键词	autophagy BF-30 I/R-injured skin flaps oxidative stress TFEB Autophagy Oxidative stress
其他关键词	PLATELET-RICH PLASMA ; CONCISE GUIDE ; CELL-DEATH ; SURVIVAL ; INFLAMMATION ; PROTECTS ; PATHWAY
摘要	Background and PurposeIschaemia-reperfusion (I/R) injury is a major contributor to skin flap necrosis, which presents a challenge in achieving satisfactory therapeutic outcomes. Previous studies showed that cathelicidin-BF (BF-30) protects tissues from I/R injury. In this investigation, BF-30 was synthesized and its role and mechanism in promoting survival of I/R-injured skin flaps explored.Experimental ApproachSurvival rate analysis and laser Doppler blood flow analysis were used to evaluate I/R-injured flap viability. Western blotting, immunofluorescence, TdT-mediated dUTP nick end labelling (TUNEL) and dihydroethidium were utilized to examine the levels of apoptosis, pyroptosis, oxidative stress, transcription factor EB (TFEB)-mediated autophagy and molecules related to the adenosine 5 '-monophosphate-activated protein kinase (AMPK)-transient receptor potential mucolipin 1 (TRPML1)-calcineurin signalling pathway.Key ResultsThe outcomes revealed that BF-30 enhanced I/R-injured island skin flap viability. Autophagy, oxidative stress, pyroptosis and apoptosis were related to the BF-30 capability to enhance I/R-injured flap survival. Improved autophagy flux and tolerance to oxidative stress promoted the inhibition of apoptosis and pyroptosis in vascular endothelial cells. Activation of TFEB increased autophagy and inhibited endothelial cell oxidative stress in I/R-injured flaps. A reduction in TFEB level led to a loss of the protective effect of BF-30, by reducing autophagy flux and increasing the accumulation of reactive oxygen species (ROS) in endothelial cells. Additionally, BF-30 modulated TFEB activity via the AMPK-TRPML1-calcineurin signalling pathway.Conclusion and ImplicationsBF-30 promotes I/R-injured skin flap survival by TFEB-mediated up-regulation of autophagy and inhibition of oxidative stress, which may have possible clinical applications. image
资助项目	National Natural Science Foundation of China; Zhejiang Province Public Welfare Technology Application Research Project [LGF20H150003]; [81801930]; [82072192]; [81873942]
出版者	WILEY
ISSN	0007-1188
EISSN	1476-5381
卷号	181 期号:7 页码:1068-1090
DOI	10.1111/bph.16268
页数	23
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001108788000001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	37850255
SCOPUSEID	2-s2.0-85178080696
通讯作者地址	[Li, Zhijie]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China ; [Zhou, Kailiang]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China ; [Ding, Jian]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,325027,China ; [Xiao, Jian]Molecular Pharmacology Research Center,School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325000,China
Scopus学科分类	Pharmacology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/205544
专题	第二临床医学院，附属第二医院、育英儿童医院药学院（分析测试中心）_分子药理研究与教学中心
通讯作者	Li, Zhijie; Xiao, Jian; Zhou, Kailiang; Ding, Jian
作者单位	1.Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China; 2.Zhejiang Provincial Key Laboratory of Orthopaedics,Wenzhou,China; 3.Molecular Pharmacology Research Center,School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China; 4.The Second Clinical Medical College of Wenzhou Medical University,Wenzhou,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; 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	第二临床医学院，附属第二医院、育英儿童医院; 药学院（分析测试中心）_分子药理研究与教学中心
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	Yang, Ningning,Yu, Gaoxiang,Lai, Yingying,et al. A snake cathelicidin enhances transcription factor EB-mediated autophagy and alleviates ROS-induced pyroptosis after ischaemia-reperfusion injury of island skin flaps[J]. BRITISH JOURNAL OF PHARMACOLOGY,2023,181(7):1068-1090.
APA	Yang, Ningning., Yu, Gaoxiang., Lai, Yingying., Zhao, Jiayi., Chen, Zhuliu., ... & Ding, Jian. (2023). A snake cathelicidin enhances transcription factor EB-mediated autophagy and alleviates ROS-induced pyroptosis after ischaemia-reperfusion injury of island skin flaps. BRITISH JOURNAL OF PHARMACOLOGY, 181(7), 1068-1090.
MLA	Yang, Ningning,et al."A snake cathelicidin enhances transcription factor EB-mediated autophagy and alleviates ROS-induced pyroptosis after ischaemia-reperfusion injury of island skin flaps".BRITISH JOURNAL OF PHARMACOLOGY 181.7(2023):1068-1090.