FGF21 promotes migration and differentiation of epidermal cells during wound healing via SIRT1-dependent autophagy

doi:10.1111/bph.15701

科研成果详情

题名	FGF21 promotes migration and differentiation of epidermal cells during wound healing via SIRT1-dependent autophagy
作者	Chen, Xixi1,2; Tong, Gaozan1; Fan, Junfu1; Shen, Yingjie1; Wang, Nan1; Gong, Wenjie 1; Hu, Zijing1; Zhu, Kunxuan 1; Li, Xiaokun1; Jin, Litai1; Cong, Weitao1; Xiao, Jian1; Zhu, Zhongxin 1
发表日期	2021-11-16
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
关键词	autophagy FGF21 keratinocyte-fibroblast interaction SIRT1 wound healing
其他关键词	CONCISE GUIDE ; PHARMACOLOGY ; KERATINOCYTES ; PGC-1-ALPHA ; METABOLISM ; ACTIVATION ; EXPRESSION ; PROTEIN ; FGF-10 ; REPAIR
摘要	Background and Purpose Migration and differentiation of epidermal cells are essential for epidermal regeneration during wound healing. Fibroblast growth factor 21 (FGF21) plays key roles in mediating a variety of biological activities. However, its role in skin wound healing remains unknown. Experimental Approach Fgf21 knockout (Fgf21 KO) mice were used to determine the effect of FGF21 on wound healing. The source of FGF21 and its target cells were determined by immunohistochemistry, immunoblotting, and ELISA assay. Moreover, Sirt1(flox/flox) and Atg7(flox/flox) mice were constructed and injected with the epidermal-specific Cre virus to elucidate the underlying mechanisms. Migration and differentiation of keratinocytes were evaluated in vitro by cell scratch assays, immunofluorescence, and qRT-RCR. The effects were further assessed when SIRT1, ATG7, ATG5, BECN1, and P53 were silenced. Interactions between SIRT1 and autophagy-related genes were assessed using immunoprecipitation assays. Key Results FGF21 was active in fibroblasts and promoted migration and differentiation of keratinocytes following injury. After wounding, SIRT1 expression and autophagosome synthesis were lower in Fgf21 KO mice. Depletion of ATG7 in keratinocytes counteracted the FGF21-induced increases in migration and differentiation, suggesting that autophagy is required for the FGF21-mediated pro-healing effects. Furthermore, epithelial-specific Sirt1 knockout abolished the FGF21-mediated improvements of autophagy and wound healing. Silencing of SIRT1 in keratinocytes, which decreased deacetylation of p53 and autophagy-related proteins, revealed that FGF21-induced autophagy during wound healing was SIRT1-dependent. Conclusions and implications FGF21 is a key regulator of keratinocyte migration and differentiation during wound healing. FGF21 may be a novel therapeutic target to accelerate would healing.
资助项目	Wenzhou Association For Science and Technology [kjfw23]; Sciences and Technology Program of Wenzhou [Y2020177]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81673077, 81770498, 81773346]
出版者	WILEY
出版地	HOBOKEN
ISSN	0007-1188
EISSN	1476-5381
卷号	179 期号:5 页码:1102-1121.
DOI	10.1111/bph.15701
页数	20
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000718938700001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	34608629
SCOPUSEID	2-s2.0-85118989679
自科自定义期刊分类	T3(B)类
通讯作者地址	[Jin, Litai]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China ; [Cong, Weitao]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China ; [Xiao, Jian]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China ; [Zhu, Zhongxin]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Pharmacology
引用统计	被引频次：6[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/3514
专题	药学院（分析测试中心）研究生工作部（研究生院）药学院（分析测试中心）_博士
通讯作者	Jin, Litai; Cong, Weitao; Xiao, Jian; Zhu, Zhongxin
作者单位	1.School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China; 2.Department of Pharmacy,Taizhou Central Hospital (Taizhou University Hospital),Taizhou,China
第一作者单位	温州医科大学
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Chen, Xixi,Tong, Gaozan,Fan, Junfu,et al. FGF21 promotes migration and differentiation of epidermal cells during wound healing via SIRT1-dependent autophagy[J]. BRITISH JOURNAL OF PHARMACOLOGY,2021,179(5):1102-1121..
APA	Chen, Xixi., Tong, Gaozan., Fan, Junfu., Shen, Yingjie., Wang, Nan., ... & Zhu, Zhongxin. (2021). FGF21 promotes migration and differentiation of epidermal cells during wound healing via SIRT1-dependent autophagy. BRITISH JOURNAL OF PHARMACOLOGY, 179(5), 1102-1121..
MLA	Chen, Xixi,et al."FGF21 promotes migration and differentiation of epidermal cells during wound healing via SIRT1-dependent autophagy".BRITISH JOURNAL OF PHARMACOLOGY 179.5(2021):1102-1121..