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Review
. 2023 Mar 10;13(3):513.
doi: 10.3390/biom13030513.

Novel Insights into the Role of Keratinocytes-Expressed TRPV3 in the Skin

Yaotao Guo  1   2 , Yajuan Song  1 , Wei Liu  1 , Tong Wang  1 , Xianjie Ma  1 , Zhou Yu  1
Affiliations
Review

Novel Insights into the Role of Keratinocytes-Expressed TRPV3 in the Skin

Yaotao Guo et al. Biomolecules. .

Abstract

TRPV3 is a non-selective cation channel that is highly expressed in keratinocytes in the skin. Traditionally, keratinocytes-expressed TRPV3 is involved in multiple physiological and pathological functions of the skin, such as itching, heat pain, and hair development. Although the underlying mechanisms by which TRPV3 functions in vivo remain obscure, recent research studies suggest that several cytokines and EGFR signaling pathways may be involved. However, there have also been other studies with opposite results that question the role of TRPV3 in heat pain. In addition, an increasing number of studies have suggested a novel role of TRPV3 in promoting skin regeneration, indicating that TRPV3 may become a new potential target for regulating skin regeneration. This paper not only reviews the role of keratinocytes-expressed TRPV3 in the physiological and pathological processes of itching, heat pain, hair development, and skin regeneration, but also reviews the relationship between TRPV3 gene mutations and skin diseases such as atopic dermatitis (AD) and Olmsted syndrome (OS). This review will lay a foundation for further developing our understanding of the mechanisms by which TRPV3 is involved in itching, heat pain, and hair development, as well as the treatments for TRPV3-related skin diseases.

Keywords: TRPV3; hair development; heat pain; itch; keratinocytes; olmsted syndrome; skin regeneration.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
TRP channel family and TRPV3 channel protein. TRP channel, transient receptor potential cation channel. TRPA, TRP channel subfamily A (ankyrin). TRPC, TRP channel subfamily C (canonical). TRPM, TRP channel subfamily M (melastatin). TRPML, TRP channel (mucolipin). TRPN, TRP channel subfamily N (Drosophila NOMPC). TRPP, TRP channel subfamily P (polycystin). TRPV, TRP channel subfamily V (vanilloid). TRPY, TRP channel subfamily Y (yeast). (TRPV3 structure image is cited from Shimada, H., Kusakizako, T., Nishizawa, T., Nureki, O. (2020) cryo-EM structure of TRPV3 in lipid nanodisc. https://doi.org/10.2210/pdb6LGP/pdb accessed on 02 February 2023).
Figure 2
Figure 2
(A) Evidence of TRPV3-mediated itching. (I) High expression and enhanced activity of the TRPV3 channel was found in itchy skin. (II) After treatment with TRPV3 agonist, the normal scar became itchy. (B) The mechanism of TRPV3-mediated itching. (I) After activation by heat stimulus or a TRPV3 agonist, activated TRPV3 provoked itching through thymic stromal lymphopoietin (TSLP), nerve growth factor (NGF), prostaglandin E2 receptor EP3 subtype-like (PGE2), and IL-33. (II) Inflammatory factors such as IL-31 induce high expression of B-type natriuretic peptide (BNP) to activate TRPV3, which leads to the upregulation of Serpin E1 and itching.
Figure 3
Figure 3
The regulatory effect of TRPV3 in hair development. Physiological TRPV3 maintains normal hair growth. Overactivated TRPV3 results in decreased proliferation, increased apoptosis, and increased differentiation of cells, as well as the hairless phenotype. TRPV3 knockout leads to hair irregularity.
Figure 4
Figure 4
Positive feedback activation of TRPV3 and EGFR. The opening of activated TRPV3 channels for Ca2+ influx leads to a surge in intracellular calcium signaling, which promotes TGF-α release. TGF-α and EGF in turn activate their receptor EGFR, which then activates ERK and PLC. ERK sensitizes TRPV3 by phosphorylation modification and PLC by hydrolyzing PIP2. TRPV3 in the sensitized state is more easily activated by stimuli. In a word, TRPV3 and EGFR form a positive feedback activation pathway.
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Grants and funding

This research was funded by the National Natural Science Foundation of China (No. 82172229, No. 81971851), Natural Science Basic Research Plan in Shaanxi Province of China (No. 2022JM-600), and the Foundation of Xijing Hospital Grants (No. XJZT21CM33).