TGF-beta 1 enhances the activity of acid-sensing ion channel in rat primary sensory neurons
TGF-beta 1 enhances the activity of acid-sensing ion channel in rat primary sensory neurons
复制标题
TGF-β1增强大鼠初级感觉神经元酸敏感离子通道的活性
DOI：
10.1002/jnr.24481
复制
发表时间：
2019
影响因子：
4.2
通讯作者：
Hu Wang Ping
中科院分区：
文献类型：
--
作者：
Qiu Chun Yu;Liu Ting Ting;Wei Shuang;Zhou Yi Mei;Wu Lei;Jin Ying;Hu Wang Ping
转化生长因子-β1（TGF-β1）是多功能生长因子超家族的重要成员。它与疼痛信号传导有关，但对其潜在机制知之甚少。在此，我们报道TGF-β1可以对大鼠背根神经节（DRG）神经元酸敏感离子通道（ASIC）的功能活性产生持续增强作用。预施加 TGF-β1 以剂量依赖性方式增加质子门控电流的幅度。尽管 TGF-β1 仅处理一次，但 ASIC 电流的增强持续了 30 分钟以上。 TGF-β1 的这种持续增强可以通过选择性 TGF-β 受体 I 拮抗剂 SD-208 的细胞外治疗来阻断，并通过阻断细胞内的几个非 Smad 信号通路来消除。 TGF-β1 还持续增强大鼠 DRG 神经元中质子诱发的尖峰。此外，TGF-β1外周预处理会剂量依赖性地加剧大鼠通过TGF-β受体I足底注射乙酸引起的伤害性行为。这些结果表明，TGF-β1 增强了 ASIC 介导的电生理活动和伤害性行为，这揭示了 TGF-β1 通过使 ASIC 敏感而参与外周疼痛信号传导的新机制。
Transforming growth factor‐β1 (TGF‐β1) is an important member of multifunctional growth factor superfamily. It has been implicated in pain signaling, but little is known about the underlying mechanisms. Herein, we report that TGF‐β1 can exert a sustained enhancing effect on the functional activity of acid‐sensing ion channels (ASICs) in rat dorsal root ganglia (DRG) neurons. Pre‐application of TGF‐β1 increased the amplitude of proton‐gated currents in a dose‐dependent manner. Enhancement of ASIC currents lasted for more than 30 min although TGF‐β1 was treated once only. This sustained enhancement by TGF‐β1 could be blocked by extracellular treatment of selective TGF‐β receptor I antagonist SD‐208, and abolished by blockade of intracellular several non‐Smad‐signaling pathways. TGF‐β1 also sustainedly enhanced proton‐evoked spikes in rat DRG neurons. Moreover, peripheral pre‐treatment with TGF‐β1 dose‐dependently exacerbated nociceptive behaviors evoked by intraplantar injection of acetic acid through TGF‐β receptor I in rats. These results suggested that TGF‐β1 potentiated ASIC‐mediated electrophysiological activity and nociceptive behaviors, which revealed a novel mechanism underlying TGF‐β1 implicated in peripheral pain signaling by sensitizing ASICs.