Open AccessFibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
Author(s) -
Lu Yingfeng,
Li Rui,
Zhu Junyi,
Wu Yanqing,
Li Duohui,
Dong Lupeng,
Li Yiyang,
Wen Xin,
Yu Fangzheng,
Zhang Hongyu,
Ni Xiao,
Du Shenghu,
Li Xiaokun,
Xiao Jian,
Wang Jian
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13952
Subject(s) - remyelination , microbiology and biotechnology , autophagy , fibroblast growth factor , mapk/erk pathway , oxidative stress , regeneration (biology) , programmed cell death , schwann cell , nerve growth factor , chemistry , cancer research , biology , kinase , endocrinology , biochemistry , myelin , apoptosis , receptor , central nervous system
Seeking for effective drugs which are beneficial to facilitating axonal regrowth and elongation after peripheral nerve injury ( PNI ) has gained extensive attention. Fibroblast growth factor 21 ( FGF 21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little concern for the potential protective effect of FGF 21 on nerve regeneration after PNI and revealing related molecular mechanisms. Here, we firstly found that exogenous FGF 21 administration remarkably promoted functional and morphologic recovery in a rat model of sciatic crush injury, manifesting as persistently improved motor and sensory function, enhanced axonal remyelination and regrowth and accelerated Schwann cells ( SC s) proliferation. Furthermore, local FGF 21 application attenuated the excessive activation of oxidative stress, which was accompanied with the activation of nuclear factor erythroid‐2‐related factor 2 (Nrf‐2) transcription and extracellular regulated protein kinases ( ERK ) phosphorylation. We detected FGF 21 also suppressed autophagic cell death in SC s. Additionally, treatment with the ERK inhibitor U0126 or autophagy inhibitor 3‐ MA partially abolishes anti‐oxidant effect and reduces SC s death. Taken together, these results indicated that the role of FGF 21 in remyelination and nerve regeneration after PNI was probably related to inhibit the excessive activation of ERK /Nrf‐2 signalling‐regulated oxidative stress and autophagy‐induced cell death. Overall, our work suggests that FGF 21 administration may provide a new therapy for PNI .