1. Biochemistry and Chemical Biology

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

  1. Qiang Liu
  2. Jin Wang
  3. Xin Wei
  4. Juan Hu
  5. Conghui Ping
  6. Yue Gao
  7. Chang Xie
  8. Peiyu Wang
  9. Peng Cao
  10. Zhengyu Cao
  11. Ye Yu
  12. Dongdong Li
  13. Jing Yao  Is a corresponding author
  1. Wuhan University, China
  2. China Pharmaceutical University, China
  3. Nanjing University of Chinese Medicine, China
  4. CNRS UMR8246, INSERM U1130, UPMC UM119, France
https://doi.org/10.7554/eLife.68128
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  1. Qiang Liu
  2. Jin Wang
  3. Xin Wei
  4. Juan Hu
  5. Conghui Ping
  6. Yue Gao
  7. Chang Xie
  8. Peiyu Wang
  9. Peng Cao
  10. Zhengyu Cao
  11. Ye Yu
  12. Dongdong Li
  13. Jing Yao
(2021)
Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine
eLife 10:e68128.
https://doi.org/10.7554/eLife.68128
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Abstract

The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.

Data availability

All the data for Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine have been deposited in Dyrad with DOI https://doi.org/10.5061/dryad.7d7wm37sq.

The following data sets were generated

Article and author information

Author details

  1. Qiang Liu

    Department of Cell Biology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Jin Wang

    School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Xin Wei

    Department of Cell Biology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Juan Hu

    Department of Cell Biology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Conghui Ping

    Department of Cell Biology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Yue Gao

    Department of Cell Biology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Chang Xie

    Department of Cell Biology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.

  8. Peiyu Wang

    Department of Cell Biology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.

  9. Peng Cao

    Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  10. Zhengyu Cao

    School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  11. Ye Yu

    School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  12. Dongdong Li

    Neuroscience Paris Seine, CNRS UMR8246, INSERM U1130, UPMC UM119, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  13. Jing Yao

    Department of Cell Biology, Wuhan University, Wuhan, China
    For correspondence
    jyao@whu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1844-3988

Funding

National Natural Science Foundation of China (31830031)

  • Jing Yao

National Natural Science Foundation of China (31929003)

  • Jing Yao

National Natural Science Foundation of China (31871174)

  • Jing Yao

National Natural Science Foundation of China (31671209)

  • Jing Yao

National Natural Science Foundation of China (31601864)

  • Jing Yao

Natural Science Foundation of Hubei Province (2017CFA063)

  • Jing Yao

Natural Science Foundation of Hubei Province (2018CFA016)

  • Jing Yao

Natural Science Foundation of Jiangsu Province (BK20202002)

  • Ye Yu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Kenton J Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Ethics

Animal experimentation: All mice were housed in the specific pathogen-free animal facility at Wuhan University and all animal experiments were in accordance with protocols were adhered to the Chinese National Laboratory Animal-Guideline for Ethical Review of Animal Welfare and approved by the Institutional Animal Care and Use Committee of Wuhan University (NO. WDSKY0201804). The mice were euthanatized with CO2 followed by various studies.

Version history

  1. Received: March 5, 2021
  2. Accepted: April 19, 2021
  3. Accepted Manuscript published: April 20, 2021 (version 1)
  4. Version of Record published: May 11, 2021 (version 2)
  5. Version of Record updated: May 13, 2021 (version 3)

Copyright

© 2021, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Qiang Liu
  2. Jin Wang
  3. Xin Wei
  4. Juan Hu
  5. Conghui Ping
  6. Yue Gao
  7. Chang Xie
  8. Peiyu Wang
  9. Peng Cao
  10. Zhengyu Cao
  11. Ye Yu
  12. Dongdong Li
  13. Jing Yao
(2021)
Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine
eLife 10:e68128.
https://doi.org/10.7554/eLife.68128

Share this article

https://doi.org/10.7554/eLife.68128

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