FGF21 inhibits ferroptosis caused by mitochondrial damage to promote the repair of peripheral nerve injury

doi:10.3389/fphar.2024.1358646

科研成果详情

题名	FGF21 inhibits ferroptosis caused by mitochondrial damage to promote the repair of peripheral nerve injury
作者	Yan, Yao1,2,3; Ran, Xinyu1,3; Zhou, Zihan 1,3; Gu, Yuting1,2,3; Wang, Rendu 1,3; Qiu, Chuanqi1,3; Sun, Yinuo1,3; Wang, Jifeng1,3; Xiao, Jian 1,2,3; Lu, Yingfeng1,3; Wang, Jian1,2,3
发表日期	2024-09-23
发表期刊	FRONTIERS IN PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	peripheral nerve injury ferroptosis mitochondria fibroblast growth factor 21 (FGF21) schwann cell ROS lipid peroxidation
其他关键词	CELL-DEATH ; SCHWANN-CELLS ; FGF-21 ; NEXUS ; IRON
摘要	Introduction Ferroptosis is a new type of cell death characterized by lipid peroxidation and iron dependency, representing an emerging disease regulation mechanism. The limited understanding of ferroptosis in peripheral nerve injury (PNI) complicates the management of such injuries. Mitochondrial dysfunction, which contributes to ferroptosis, further exacerbates the challenges of peripheral nerve repairMethods In this study, we established an in vitro model of Schwann cells model treated with TBHP and an in vivo sciatic nerve crush injury model in rats. These models were used to investigate the effects of fibroblast growth factor 21 (FGF21) on PNI, both in vitro and in vivo, and to explore the potential mechanisms linking injury-induced ferroptosis and mitochondrial dysfunction.Results Our findings reveal that PNI triggers abnormal accumulation of lipid reactive oxygen species (ROS) and inactivates mitochondrial respiratory chain complex III, leading to mitochondrial dysfunction. This dysfunction catalyzes the oxidation of excessive polyunsaturated fatty acids, resulting in antioxidant imbalance and loss of ferroptosis suppressor protein 1 (FSP1), which drives lipid peroxidation. Additionally, irregular iron metabolism, defective mitophagy, and other factors contribute to the induction of ferroptosis. Importantly, we found that FGF21 attenuates the abnormal accumulation of lipid ROS, restores mitochondrial function, and suppresses ferroptosis, thus promoting PNI repair. Notably, glutathione peroxidase 4 (GPX4), a downstream target of nuclear factor E2-related factor 2 (Nrf2), and the ERK/Nrf2 pathway are involved in the regulation of ferroptosis by FGF21.Conclusion FGF21 promotes peripheral nerve repair by inhibiting ferroptosis caused by mitochondrial dysfunction. Therefore, targeting mitochondria and ferroptosis represents a promising therapeutic strategy for effective PNI repair.
资助项目	National Natural Science Foundation of China [82171375]
出版者	FRONTIERS MEDIA SA
EISSN	1663-9812
卷号	15
DOI	10.3389/fphar.2024.1358646
页数	22
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001326733400001
收录类别	SCIE
PubMed ID	39376607
通讯作者地址	[Wang, Jian]Wenzhou Med Univ, Dept Wound Repair, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China. ; [Wang, Jian]Wenzhou Med Univ, Cixi Biomed Res Inst, Wenzhou, Zhejiang, Peoples R China. ; [Wang, Jian]Wenzhou Med Univ, Wenzhou, Zhejiang, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/220810
专题	附属第一医院温州医科大学其他_温州医科大学慈溪生物医药研究院
通讯作者	Wang, Jian
作者单位	1.Wenzhou Med Univ, Dept Wound Repair, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Cixi Biomed Res Inst, Wenzhou, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Wenzhou, Zhejiang, Peoples R China
第一作者单位	附属第一医院; 其他_温州医科大学慈溪生物医药研究院; 温州医科大学
通讯作者单位	附属第一医院; 其他_温州医科大学慈溪生物医药研究院; 温州医科大学
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Yan, Yao,Ran, Xinyu,Zhou, Zihan,et al. FGF21 inhibits ferroptosis caused by mitochondrial damage to promote the repair of peripheral nerve injury[J]. FRONTIERS IN PHARMACOLOGY,2024,15.
APA	Yan, Yao., Ran, Xinyu., Zhou, Zihan., Gu, Yuting., Wang, Rendu., ... & Wang, Jian. (2024). FGF21 inhibits ferroptosis caused by mitochondrial damage to promote the repair of peripheral nerve injury. FRONTIERS IN PHARMACOLOGY, 15.
MLA	Yan, Yao,et al."FGF21 inhibits ferroptosis caused by mitochondrial damage to promote the repair of peripheral nerve injury".FRONTIERS IN PHARMACOLOGY 15(2024).