Upregulation of DRG protein TMEM100 facilitates dry-skin-induced pruritus by enhancing TRPA1 channel function.
Upregulation of DRG protein TMEM100 facilitates dry-skin-induced pruritus by enhancing TRPA1 channel function.
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DOI：
10.3724/abbs.2022180
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发表时间：
2022-12-25
影响因子：
3.7
通讯作者：
Wen D
中科院分区：
文献类型：
--
作者：
Pan C;Jiao Y;Kong D;Deng H;Xu S;Tang D;Yin W;Gao P;Yu W;Fan Y;Wen D
干燥的皮肤折磨着许多严重瘙痒的患者。瞬时受体电位阳离子通道V成员1（TRPV 1）和A成员1（TRPA 1）是外周神经编码瘙痒感觉的两个必需受体，分别介导组胺能和非组胺能瘙痒。在背根神经节中，跨膜蛋白100（TMEM 100）在结构上与TRPV 1和TRPA 1受体相关，但TMEM 100在瘙痒感觉编码中的确切作用仍然未知。在这里，在这项研究中，我们发现，TMEM 100 + DRG神经元占丙酮-乙醚-水（AEW）诱导的干燥皮肤瘙痒模型中的大多数激活的神经元，一些TMEM 100 + DRG神经元与TRPA 1和氯喹相关的Mrgpr瘙痒受体家族共定位。TRPA 1通道的表达和功能在AEW模型中均上调，而TRPV 1通道未上调，并且特异性DRG Tmem 100基因敲低可抑制AEW诱导的瘙痒并挽救TRPA 1的表达和功能变化。我们的研究结果有力地表明，TMEM 100蛋白在DRG是主要的促进因素，在DRG中的TMEM 100的特异性抑制可能是一种新的有效的治疗策略，为患者遭受干燥皮肤引起的瘙痒。
The dry skin tortures numerous patients with severe itch. The transient receptor potential cation channel V member 1 (TRPV1) and A member 1 (TRPA1) are two essential receptors for peripheral neural coding of itch sensory, mediating histaminergic and nonhistaminergic itch separately. In the dorsal root ganglion, transmembrane protein 100 (TMEM100) is structurally related to both TRPV1 and TRPA1 receptors, but the exact role of TMEM100 in itch sensory coding is still unknown. Here, in this study, we find that TMEM100 + DRG neurons account for the majority of activated neurons in an acetone-ether-water (AEW)-induced dry skin itch model, and some TMEM100 + DRG neurons are colocalized with both TRPA1 and the chloroquine-related Mrgpr itch receptor family. Both the expression and function of TRPA1 channels, but not TRPV1 channels, are upregulated in the AEW model, and specific DRG Tmem100 gene knockdown alleviates AEW-induced itch and rescues the expression and functional changes of TRPA1. Our results strongly suggest that TMEM100 protein in DRG is the main facilitating factor for dry skin-related chronic itch, and specific suppression of TMEM100 in DRG could be a novel effective treatment strategy for patients who suffer from dry skin-induced itch.
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影响因子：
2.7
作者：
Lin SY;Zhang SZ;An JX;Qian XY;Gao XY;Wang Y;Zhao WX;Eastwood D;Cope DK;Williams JP
通讯作者：
Williams JP
影响因子：
3.6
作者：
通讯作者：
--
影响因子：
4.2
作者：
He, Qian;Dong, Yilin;He, Yujuan
通讯作者：
He, Yujuan
DOI：
10.1126/science.1174868
发表时间：
2009-09-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Sun YG;Zhao ZQ;Meng XL;Yin J;Liu XY;Chen ZF
通讯作者：
Chen ZF
影响因子：
21.1
作者：
Gouin O;L'Herondelle K;Lebonvallet N;Le Gall-Ianotto C;Sakka M;Buhé V;Plée-Gautier E;Carré JL;Lefeuvre L;Misery L;Le Garrec R
通讯作者：
Le Garrec R