Upregulation of DRG protein TMEM100 facilitates dryskin-induced pruritus by enhancing TRPA1 channel function
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 ro...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
China Science Publishing & Media Ltd.
2022-12-01
|
| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022180 |
| _version_ | 1797635794947538944 |
|---|---|
| author | Pan Chao Jiao Yingfu Kong Dexu Deng Haoyue Xu Saihong Tang Dan Yin Wen Gao Po Yu Weifeng Fan Yinghui Wen Daxiang |
| author_facet | Pan Chao Jiao Yingfu Kong Dexu Deng Haoyue Xu Saihong Tang Dan Yin Wen Gao Po Yu Weifeng Fan Yinghui Wen Daxiang |
| author_sort | Pan Chao |
| collection | DOAJ |
| description | 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 <sup>+</sup> DRG neurons account for the majority of activated neurons in an acetone-ether-water (AEW)-induced dry skin itch model, and some TMEM100 <sup>+</sup> 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. |
| first_indexed | 2024-03-11T12:26:25Z |
| format | Article |
| id | doaj.art-2054f16cbc64467b923c03005e40389a |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:26:25Z |
| publishDate | 2022-12-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-2054f16cbc64467b923c03005e40389a2023-11-06T08:51:46ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-12-015540441610.3724/abbs.202218020d259ccUpregulation of DRG protein TMEM100 facilitates dryskin-induced pruritus by enhancing TRPA1 channel functionPan Chao0Jiao Yingfu1Kong Dexu2Deng Haoyue3Xu Saihong4Tang Dan5Yin Wen6Gao Po7Yu Weifeng8Fan Yinghui9Wen Daxiang10[][][][][][][][][][][]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 <sup>+</sup> DRG neurons account for the majority of activated neurons in an acetone-ether-water (AEW)-induced dry skin itch model, and some TMEM100 <sup>+</sup> 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. https://www.sciengine.com/doi/10.3724/abbs.2022180dry skin-induced itchTMEM100TRPA1TRPV1DRG |
| spellingShingle | Pan Chao Jiao Yingfu Kong Dexu Deng Haoyue Xu Saihong Tang Dan Yin Wen Gao Po Yu Weifeng Fan Yinghui Wen Daxiang Upregulation of DRG protein TMEM100 facilitates dryskin-induced pruritus by enhancing TRPA1 channel function Acta Biochimica et Biophysica Sinica dry skin-induced itch TMEM100 TRPA1 TRPV1 DRG |
| title | Upregulation of DRG protein TMEM100 facilitates dryskin-induced pruritus by enhancing TRPA1 channel function |
| title_full | Upregulation of DRG protein TMEM100 facilitates dryskin-induced pruritus by enhancing TRPA1 channel function |
| title_fullStr | Upregulation of DRG protein TMEM100 facilitates dryskin-induced pruritus by enhancing TRPA1 channel function |
| title_full_unstemmed | Upregulation of DRG protein TMEM100 facilitates dryskin-induced pruritus by enhancing TRPA1 channel function |
| title_short | Upregulation of DRG protein TMEM100 facilitates dryskin-induced pruritus by enhancing TRPA1 channel function |
| title_sort | upregulation of drg protein tmem100 facilitates dryskin induced pruritus by enhancing trpa1 channel function |
| topic | dry skin-induced itch TMEM100 TRPA1 TRPV1 DRG |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022180 |
| work_keys_str_mv | AT panchao upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT jiaoyingfu upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT kongdexu upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT denghaoyue upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT xusaihong upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT tangdan upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT yinwen upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT gaopo upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT yuweifeng upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT fanyinghui upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction AT wendaxiang upregulationofdrgproteintmem100facilitatesdryskininducedpruritusbyenhancingtrpa1channelfunction |