Miswiring of Merkel cell and pruriceptive C fiber drives the itch-scratch cycle.
Miswiring of Merkel cell and pruriceptive C fiber drives the itch-scratch cycle.
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DOI：
10.1126/scitranslmed.abn4819
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发表时间：
2022-07-13
影响因子：
17.1
通讯作者：
Hu, Hongzhen
中科院分区：
文献类型：
--
作者：
Feng, Jing;Zhao, Yonghui;Xie, Zili;Zang, Kaikai;Sviben, Sanja;Hu, Xueming;Fitzpatrick, James A. J.;Wen, Lu;Liu, Yifei;Wang, Ting;Lawson, Katy;Liu, Qin;Yan, Yan;Dong, Xinzhong;Han, Liang;Wu, Gregory F.;Kim, Brian S.;Hu, Hongzhen
痒的感觉激发抓反射，以保护我们免受皮肤上有害的刺激。虽然抓挠通过激活机械感受器暂时缓解急性瘙痒，但随着时间的推移，它会进一步加剧慢性瘙痒的恶性瘙痒-抓挠循环。虽然在临床上得到了很好的认识，但瘙痒-抓伤循环背后的外周机制仍然知之甚少。在这里，我们展示了皮肤的机械刺激导致默克尔细胞上的Piezo2通道的激活，这在病理上促进了实验性干燥皮肤的自发瘙痒。三维重建和免疫电镜显示，在皮肤干燥的情况下，MRGPRA3+ pricreceptor神经末梢指向Merkel细胞的结构改变。我们的研究结果揭示了病理条件下的功能性错误连接机制，导致触觉感受器触发皮肤中瘙痒感受器的放电，从而驱动瘙痒-抓伤循环。上皮性触觉受体的病理性错误连接导致感觉触觉受体的适应性激活，从而传播瘙痒-抓痒循环。
Itch sensation provokes the scratch reflex to protect us from harmful stimuli in the skin. Although scratching transiently relieves acute itch through activation of mechanoreceptors, it propagates the vicious itch-scratch cycle in chronic itch by further aggravating itch over time. Although well recognized clinically, the peripheral mechanisms underlying the itch-scratch cycle remain poorly understood. Here we show that mechanical stimulation of the skin results in activation of the Piezo2 channels on Merkel cells that pathologically promotes spontaneous itch in experimental dry skin. Three-dimensional reconstruction and immunoelectron microscopy revealed structural alteration of MRGPRA3+ pruriceptor nerve endings directed towards Merkel cells in the setting of dry skin. Our results uncover a functional miswiring mechanism under pathologic conditions, resulting in touch receptors triggering the firing of pruriceptors in the skin to drive the itch-scratch cycle. A pathologic miswiring in the epithelial touch receptor results in adaptive activation of sensory pruriceptor to propagate the itch-scratch cycle.
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炎性瘙痒和疼痛模型中 MRGPRA3 和 MRGPRD 阳性伤害感受器的兴奋性增强
影响因子：
14.5
作者：
Qu, Lintao;Fan, Ni;LaMotte, Robert H.
通讯作者：
LaMotte, Robert H.
DOI：
10.1016/j.jaci.2017.05.051
发表时间：
2018-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Luo J;Feng J;Yu G;Yang P;Mack MR;Du J;Yu W;Qian A;Zhang Y;Liu S;Yin S;Xu A;Cheng J;Liu Q;O'Neil RG;Xia Y;Ma L;Carlton SM;Kim BS;Renner K;Liu Q;Hu H
通讯作者：
Hu H
影响因子：
8.8
作者：
Prato V;Taberner FJ;Hockley JRF;Callejo G;Arcourt A;Tazir B;Hammer L;Schad P;Heppenstall PA;Smith ES;Lechner SG
通讯作者：
Lechner SG
影响因子：
3
作者：
Nojima, H;Carstens, E
通讯作者：
Carstens, E
DOI：
10.1007/978-3-662-44605-8_10
发表时间：
2015-01-01
期刊：
PHARMACOLOGY OF ITCH
影响因子：
--
作者：
Schwendinger-Schreck, Jamie;Wilson, Sarah R.;Bautista, Diana M.
通讯作者：
Bautista, Diana M.