Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death.
Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death.
复制标题
成纤维细胞生长因子 21 通过抑制氧化损伤和自噬性细胞死亡来促进周围神经再生。
DOI：
10.1111/jcmm.13952
复制
发表时间：
2019-01
影响因子：
5.3
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Lu Y;Li R;Zhu J;Wu Y;Li D;Dong L;Li Y;Wen X;Yu F;Zhang H;Ni X;Du S;Li X;Xiao J;Wang J
寻找有效的促进周围神经损伤后轴突再生和伸长的药物已受到广泛关注。成纤维细胞生长因子21（FGF 21）是调节血糖和脂质稳态的代谢因子。然而，很少有人关注FGF 21对PNI后神经再生的潜在保护作用，并揭示相关的分子机制。在此，我们首次发现外源性FGF 21给药显著促进大鼠坐骨挤压伤模型的功能和形态恢复，表现为持续改善运动和感觉功能，增强轴突髓鞘再生和再生，加速雪旺细胞（SC）增殖。此外，局部应用FGF 21减弱了氧化应激的过度激活，这伴随着核因子红细胞-2相关因子2（Nrf-2）转录和细胞外调节蛋白激酶（ERK）磷酸化的激活。我们检测到FGF 21也抑制SC中的自噬细胞死亡。此外，用ERK抑制剂U 0126或自噬抑制剂3-MA治疗部分消除了抗氧化作用并减少了SC死亡。综上所述，这些结果表明，FGF 21在PNI后髓鞘再生和神经再生中的作用可能与抑制ERK/Nrf-2信号调节的氧化应激和自噬诱导的细胞死亡的过度激活有关。总体而言，我们的工作表明，FGF 21给药可能为PNI提供一种新的治疗方法。
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.
登录
查看更多内容
FGF21 在创伤性脑损伤后通过 FGFR1/β-Klotho 上调 PPARγ 来保护血脑屏障
影响因子：
4.2
作者：
Chen, Jun;Hu, Jian;Lin, Li
通讯作者：
Lin, Li
影响因子：
3.5
作者：
Hota, Kalpana Barhwal;Hota, Sunil Kumar;Singh, Shashi Bala
通讯作者：
Singh, Shashi Bala
影响因子：
3.6
作者：
Itoh, Nobuyuki
通讯作者：
Itoh, Nobuyuki
Nrf2 的上调参与 FGF21 介导的非诺贝特对 1 型糖尿病肾病的保护作用。
影响因子：
7.4
作者：
Cheng Y;Zhang J;Guo W;Li F;Sun W;Chen J;Zhang C;Lu X;Tan Y;Feng W;Fu Y;Liu GC;Xu Z;Cai L
通讯作者：
Cai L
影响因子：
168.9
作者：
Fu, XB;Shen, ZY;Sheng, ZY
通讯作者：
Sheng, ZY