TRPV3, short for Transient receptor potential vanillin 3, is a Ca²⁺ -permeable nonselective cation channel and a member of the transient receptor potential (TRP) superfamily [1,2,3]. It can recognize thermal stimulation (31-39 °C) and is highly expressed in skin keratinocytes and peripheral neurons. TRPV3 plays a crucial role in temperature perception, pain transduction, skin physiology, inflammation, and is associated with diseases like cancer, atopic dermatitis, and acne [1,2,4,5]. It participates in signaling pathways related to itch, dermatitis, hair growth, and skin regeneration [2]. Genetic mouse models have been instrumental in understanding its functions [3].

Gain-of-function genetic mutations of TRPV3 in rodents have been crucial in unveiling its role in skin health and disease. For example, in Trpv3+/G568V mice (a gain-of-function model), TRPV3-activated PARP1/AIFM1/MIF axis through oxidative stress contributes to atopic dermatitis, and inhibiting PARP1 can alleviate the symptoms [4]. In acne-like mice, TRPV3 expression increases in skin lesions, and its inhibition alleviates acne-like skin inflammation, suggesting its role in acne development [5]. Also, in mouse models, the interaction between TRPV3 and ANO1 positively regulates wound healing in keratinocytes, as blockers of either channel inhibit cell migration and proliferation [6].

In conclusion, TRPV3 is essential for multiple biological functions, especially in skin-related processes. The study of TRPV3 using mouse models, including those with gain-of-function mutations, has significantly enhanced our understanding of its role in diseases such as atopic dermatitis and acne. These findings may provide potential therapeutic targets for treating these skin-related disorders.

References:

1. Su, Wuyue, Qiao, Xue, Wang, Wumei, Liang, Ke, Hong, Xuechuan. 2023. TRPV3: Structure, Diseases and Modulators. In Molecules (Basel, Switzerland), 28, . doi:10.3390/molecules28020774. https://pubmed.ncbi.nlm.nih.gov/36677834/

2. Kalinovskii, Aleksandr P, Utkina, Lyubov L, Korolkova, Yuliya V, Andreev, Yaroslav A. 2023. TRPV3 Ion Channel: From Gene to Pharmacology. In International journal of molecular sciences, 24, . doi:10.3390/ijms24108601. https://pubmed.ncbi.nlm.nih.gov/37239947/

3. Yang, Pu, Zhu, Michael X. . TRPV3. In Handbook of experimental pharmacology, 222, 273-91. doi:10.1007/978-3-642-54215-2_11. https://pubmed.ncbi.nlm.nih.gov/24756710/

4. Song, Zhongya, Gao, Meng, Li, Tianxiao, Yao, Xu, Yang, Yong. 2024. TRPV3-Activated PARP1/AIFM1/MIF Axis through Oxidative Stress Contributes to Atopic Dermatitis. In The Journal of investigative dermatology, 144, 2695-2705.e8. doi:10.1016/j.jid.2024.04.020. https://pubmed.ncbi.nlm.nih.gov/38823435/

5. Wei, Ziyu, Gao, Meng, Liu, Yihe, Li, Ji, Yang, Yong. 2024. TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 167195. doi:10.1016/j.bbadis.2024.167195. https://pubmed.ncbi.nlm.nih.gov/38648901/

6. Yamanoi, Yu, Lei, Jing, Takayama, Yasunori, Marunaka, Yoshinori, Tominaga, Makoto. 2023. TRPV3-ANO1 interaction positively regulates wound healing in keratinocytes. In Communications biology, 6, 88. doi:10.1038/s42003-023-04482-1. https://pubmed.ncbi.nlm.nih.gov/36690845/