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Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death

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 (FGF21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little c...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307793/
https://www.ncbi.nlm.nih.gov/pubmed/30450828
http://dx.doi.org/10.1111/jcmm.13952
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author 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
author_facet 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
author_sort Lu, Yingfeng
collection PubMed
description 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 (FGF21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little concern for the potential protective effect of FGF21 on nerve regeneration after PNI and revealing related molecular mechanisms. Here, we firstly found that exogenous FGF21 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 (SCs) proliferation. Furthermore, local FGF21 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 FGF21 also suppressed autophagic cell death in SCs. Additionally, treatment with the ERK inhibitor U0126 or autophagy inhibitor 3‐MA partially abolishes anti‐oxidant effect and reduces SCs death. Taken together, these results indicated that the role of FGF21 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 FGF21 administration may provide a new therapy for PNI.
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spelling pubmed-63077932019-01-04 Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death 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 J Cell Mol Med Original Articles 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 (FGF21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little concern for the potential protective effect of FGF21 on nerve regeneration after PNI and revealing related molecular mechanisms. Here, we firstly found that exogenous FGF21 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 (SCs) proliferation. Furthermore, local FGF21 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 FGF21 also suppressed autophagic cell death in SCs. Additionally, treatment with the ERK inhibitor U0126 or autophagy inhibitor 3‐MA partially abolishes anti‐oxidant effect and reduces SCs death. Taken together, these results indicated that the role of FGF21 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 FGF21 administration may provide a new therapy for PNI. John Wiley and Sons Inc. 2018-11-18 2019-01 /pmc/articles/PMC6307793/ /pubmed/30450828 http://dx.doi.org/10.1111/jcmm.13952 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
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
Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
title Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
title_full Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
title_fullStr Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
title_full_unstemmed Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
title_short Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
title_sort fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307793/
https://www.ncbi.nlm.nih.gov/pubmed/30450828
http://dx.doi.org/10.1111/jcmm.13952
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