MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel.
MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel.
复制标题
DOI：
10.1016/j.celrep.2023.112283
复制
发表时间：
2023-04-25
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
虽然触觉和瘙痒是由不同的神经元群编码的，但在外源性瘙痒原存在的情况下，轻触也会引起瘙痒，导致一种称为异位现象。然而，瘙痒原引起的机械痒致敏的细胞和分子机制尚不清楚。在这里，我们发现皮内注射组胺或氯喹（CQ）通过激活表达TRPV1-和mrgpra3的瘙痒受体来刺激同种异体，这些神经元的功能消融逆转了瘙痒素诱导的同种异体。此外，表达mrgpra3的瘙痒受体的机械敏感的Piezo2通道功能的基因消融也抑制了瘙痒素诱导的异位。从机制上讲，组胺和CQ通过激活磷脂酶C （PLC）和蛋白激酶C-δ (PKCδ)信号，至少部分地使Piezo2通道功能增敏。总的来说，我们的数据发现TRPV1+/MrgprA3+瘙痒受体- piezo2信号轴在皮肤瘙痒原诱导的机械痒致敏的启动中起作用。Lu等人的研究表明，TRPV1+/MrgprA3+搔痒受体表达的机械敏感性Piezo2有助于搔痒素诱导的异位。具体来说，他们的研究结果揭示了瘙痒原激活的PLC-PKCδ信号通路，该通路使Piezo2通道功能增敏，从而在机械刺激下产生MrgprA3+瘙痒受体的超敏反应。
Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, through activation of the phospholipase C (PLC) and protein kinase C-δ (PKCδ) signaling. Collectively, our data find a TRPV1+/MrgprA3+ prurioceptor-Piezo2 signaling axis in the initiation of pruritogen-induced mechanical itch sensitization in the skin. Lu et al. showed that mechanosensitive Piezo2 expressed by the TRPV1+/MrgprA3+ pruriceptors contributes to pruritogen-induced alloknesis. Specifically, their results uncover a pruritogen-activated PLC-PKCδ signaling pathway that sensitizes Piezo2 channel function to produce hypersensitivity in MrgprA3+ pruriceptors in response to mechanical stimulation.
登录
查看更多内容
DOI：
10.1126/science.aac8653
发表时间：
2015-10-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bourane S;Duan B;Koch SC;Dalet A;Britz O;Garcia-Campmany L;Kim E;Cheng L;Ghosh A;Ma Q;Goulding M
通讯作者：
Goulding M
影响因子：
4.6
作者：
Hossain MZ;Ando H;Unno S;Kitagawa J
通讯作者：
Kitagawa J
TRPV1 和 PLC 参与组胺 H4 受体诱导的瘙痒。
影响因子：
3.1
作者：
Jian T;Yang N;Yang Y;Zhu C;Yuan X;Yu G;Wang C;Wang Z;Shi H;Tang M;He Q;Lan L;Wu G;Tang Z
通讯作者：
Tang Z
DOI：
10.1523/jneurosci.3509-12.2012
发表时间：
2012-10-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Liu Q;Sikand P;Ma C;Tang Z;Han L;Li Z;Sun S;LaMotte RH;Dong X
通讯作者：
Dong X
影响因子：
2.9
作者：
Le Pichon CE;Chesler AT
通讯作者：
Chesler AT