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Research ArticleCellular and Molecular

Pharmacological Activation of Thermo–Transient Receptor Potential Vanilloid 3 Channels Inhibits Hair Growth by Inducing Cell Death of Hair Follicle Outer Root Sheath

Kangjiao Yan, Xiaoying Sun, Gongxin Wang, Yani Liu and KeWei Wang
Journal of Pharmacology and Experimental Therapeutics August 2019, 370 (2) 299-307; DOI: https://doi.org/10.1124/jpet.119.258087
Kangjiao Yan
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China
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Xiaoying Sun
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China
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Gongxin Wang
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China
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Yani Liu
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China
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KeWei Wang
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China
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This article has a correction. Please see:

  • Correction to “Pharmacological Activation of Thermo–Transient Receptor Potential Vanilloid 3 Channels Inhibits Hair Growth by Inducing Cell Death of Hair Follicle Outer Root Sheath” - March 01, 2020

Abstract

Hair growth starts from hair follicles that reside in dermis, and abnormal hair growth is an early sign of hair follicle disease or systemic illness such as alopecia or hair loss. Therefore, identifying a target critical for dysfunctional hair follicles is fundamental to alleviating dermatologic or systemic diseases with hair abnormalities. The warm temperature–activated Ca2+-permeable transient receptor potential vanilloid 3 (TRPV3) channel protein is abundantly expressed in the skin keratinocytes, and dysfunctional TRPV3 causes human congenital Olmsted syndrome, characterized by skin diseases and alopecia, indicating an important role for TRPV3 in hair follicle development and hair growth. To validate TRPV3 as a therapeutic target, we investigated the impact of pharmacological modulation of TRPV3 on hair growth using a combination of biochemical and cell biology, immunohistochemical, whole-cell patch clamp, RNA interference, and pharmacological approaches. We found that functional TRPV3 channel proteins are highly expressed in hair follicle outer root sheath (ORS) cells as detected by Western blot analysis, immunohistochemical staining, and electrophysiological techniques. Pharmacological activation of TRPV3 by agonist natural carvacrol induces cell death of ORS cells, and topical application of carvacrol to mouse dorsal skin also inhibits hair growth. Conversely, specific inhibition of TRPV3 by inhibitor natural forsythoside B and short-hairpin RNA reverses the cell death induced by carvacrol-mediated TRPV3 activation in human ORS cells. Furthermore, forsythoside B results in a significant reversal of hair growth inhibition induced by agonist carvacrol. Altogether, our findings demonstrate that TRPV3 channel is critical for regulation of hair growth, and inhibition of TRPV3 may represent a promising therapy for hair loss or hair follicle–related skin diseases.

Footnotes

    • Received March 13, 2019.
    • Accepted May 30, 2019.
  • ↵1 K.Y. and X.S. contributed equally to this work.

  • This project was supported by grants awarded to K.W. from National Natural Sciences Foundation of China [81573410] and the Ministry of Science and Technology of China [2018ZX09711001-004-006], and a grant awarded to X.S. from Shandong Provincial Natural Science Foundation of China [ZR2017BH020].

  • https://doi.org/10.1124/jpet.119.258087.

  • Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 370 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 370, Issue 2
1 Aug 2019
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Research ArticleCellular and Molecular

Activation of TRPV3 Inhibits Hair Growth

Kangjiao Yan, Xiaoying Sun, Gongxin Wang, Yani Liu and KeWei Wang
Journal of Pharmacology and Experimental Therapeutics August 1, 2019, 370 (2) 299-307; DOI: https://doi.org/10.1124/jpet.119.258087

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Research ArticleCellular and Molecular

Activation of TRPV3 Inhibits Hair Growth

Kangjiao Yan, Xiaoying Sun, Gongxin Wang, Yani Liu and KeWei Wang
Journal of Pharmacology and Experimental Therapeutics August 1, 2019, 370 (2) 299-307; DOI: https://doi.org/10.1124/jpet.119.258087
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