Fibroblast growth factor 13 stabilizes microtubules to promote Na(+) channel function in nociceptive DRG neurons and modulates inflammatory pain.
Fibroblast growth factor 13 stabilizes microtubules to promote Na(+) channel function in nociceptive DRG neurons and modulates inflammatory pain.
复制标题
成纤维细胞生长因子 13 稳定微管，促进伤害性 DRG 神经元中的 Na 通道功能并调节炎性疼痛
DOI：
10.1016/j.jare.2020.12.009
复制
发表时间：
2021-07
影响因子：
10.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Wang Q;Yang J;Wang H;Shan B;Yin C;Yu H;Zhang X;Dong Z;Yu Y;Zhao R;Liu B;Zhang H;Wang C
成纤维细胞生长因子同源因子（FHF），在其他成纤维细胞生长因子中，越来越多地被发现是离子通道功能的重要调节剂。尽管FHF与一些神经元疾病和心律失常有关，但其在炎症性疼痛中的作用仍不清楚。本研究旨在探讨FGF 13在炎症痛中的作用及其机制。制备Fgf 13条件性基因敲除小鼠，建立CFA诱导的慢性炎性疼痛模型，测定痛阈。采用免疫组化、western blot和实时定量逆转录PCR（qRT-PCR）方法检测CFA诱导的炎性疼痛中FGF 13的表达。采用全细胞膜片钳技术记录DRG神经元动作电位放电特性和钠电流。在背根神经节（DRG）神经元中条件性敲除Fgf 13（Fgf 13-/Y）导致完全弗氏佐剂（CFA）诱导的疼痛反应减弱。FGF 13主要表达于小直径DRG神经元。CFA处理导致伤害性DRG神经元中FGF 13蛋白表达增加以及兴奋性增加，当FGF 13不存在时，所述伤害性DRG神经元的兴奋性被抑制。FGF 13在DRG神经元兴奋性中的作用与其对微管介导的电压门控Na+通道的调节有关。FGF 13的过表达，而不是缺乏结合和稳定微管能力的FGF 13突变体，挽救了Fgf 13-/Y小鼠DRG神经元中降低的神经元兴奋性和Na+电流密度。这项研究表明，FGF 13可以稳定微管，以调节背根神经节神经元的钠通道功能并调节炎症性疼痛。该研究为FGF 13调节钠通道功能提供了一种新的机制，并表明FGF 13可能是炎性疼痛治疗的新靶点。
Fibroblast growth factor homologous factors (FHFs), among other fibroblast growth factors, are increasingly found to be important regulators of ion channel functions. Although FHFs have been link to several neuronal diseases and arrhythmia, its role in inflammatory pain still remains unclear. This study aimed to investigate the role and mechanism of FGF13 in inflammatory pain. Fgf13 conditional knockout mice were generated and CFA-induced chronic inflammatory pain model was established to measure the pain threshold. Immunostaining, western blot and quantitative real-time reverse transcription PCR (qRT-PCR) were performed to detect the expression of FGF13 in CFA-induced inflammatory pain. Whole-cell patch clamp recording was used to record the action potential firing properties and sodium currents of DRG neurons. Conditional knockout of Fgf13 in dorsal root ganglion (DRG) neurons (Fgf13-/Y) led to attenuated pain responses induced by complete Freund's adjuvant (CFA). FGF13 was expressed predominantly in small-diameter DRG neurons. CFA treatment resulted in an increased expression of FGF13 proteins as well as an increased excitability in nociceptive DRG neurons which was inhibited when FGF13 was absent. The role of FGF13 in neuronal excitability of DRG was linked to its modulation of voltage-gated Na+ channels mediated by microtubules. Overexpression of FGF13, but not FGF13 mutant which lacks the ability to bind and stabilize microtubules, rescued the decreased neuronal excitability and Na+ current density in DRG neurons of Fgf13-/Y mice. This study revealed that FGF13 could stabilize microtubules to modulate sodium channel function in DRG neurons and modulate inflammatory pain. This study provides a novel mechanism for FGF13 modulation of sodium channel function and suggests that FGF13 might be a novel target for inflammatory pain treatment.
登录
查看更多内容
DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
通讯作者：
Samad TA
影响因子：
1.7
作者：
Li, GD;Wo, Y;Zhang, X
通讯作者：
Zhang, X
影响因子：
5.3
作者：
Wittmack, EK;Rush, AM;Dib-Hajj, SD
通讯作者：
Dib-Hajj, SD
FGF12 是 Brugada 综合征的候选基因座。
影响因子：
5.5
作者：
Hennessey, Jessica A.;Marcou, Cherisse A.;Wang, Chuan;Wei, Eric Q.;Wang, Chaojian;Tester, David J.;Torchio, Margherita;Dagradi, Federica;Crotti, Lia;Schwartz, Peter J.;Ackerman, Michael J.;Pitt, Geoffrey S.
通讯作者：
Pitt, Geoffrey S.
影响因子：
20.1
作者：
Wang C;Hennessey JA;Kirkton RD;Wang C;Graham V;Puranam RS;Rosenberg PB;Bursac N;Pitt GS
通讯作者：
Pitt GS