Transient Receptor Potential channels, TRPV1 and TRPA1 in melanocytes synergize UV‐dependent and UV‐independent melanogenesis

Jia, Qi; Tian, Weifeng; Li, Binbin; Chen, Wen; Zhang, Wenjie; Xie, Yang; Cheng, Na; Chen, Qi; Xiao, Jianru; Zhang, Yiwang; Yang, Jian; Wang, Shu

doi:10.1111/bph.15643

Cited by 8 publications

(3 citation statements)

References 54 publications

(167 reference statements)

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“…Hence, agreeing with our results, inhibition of TRPA1 seem to have a miner effect on the protein expression of gp100, but a major effect on melanin content. Additionally, in 2021, Jia et al 37 found that PUVA‐induced melanogenesis required TRPV1‐ and TRPA1‐mediated Ca 2+ influx in melanocytes. Consistent with this, our results also revealed a corresponding increase or decrease in UVB‐induced skin pigmentation with activation or inhibition of TRPA1 in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, agreeing with our results, inhibition of TRPA1 seem to have a miner effect on the protein expression of gp100, but a major effect on melanin content. Additionally, in 2021, Jia et al 37 ] im and the biological responses in melanosomes. 39 In 2016, Ambrosio et al 30 proposed that knockout of the gene encoded twopore channel 2 (TPC2) protein, a cation release channel expressed in the melanosome-limiting membrane in human melanocytes, produced a decrease of the peri-melanosomes calcium concentration and an increase in melanosome luminal pH, eliciting a significant increase in melanin content and larger size of melanosomes.…”

Section: Topical Treatment With Trpa1 Specific Antagonist Hc-030031 M...mentioning

confidence: 99%

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TRPA1 promotes UVB‐induced skin pigmentation by regulating melanosome luminal pH

Wang

Liu

et al. 2022

Experimental Dermatology

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Melanocytes stimulated by ultraviolet radiation (UVR) produce melanin and melanosomes, which causes skin pigmentation and acts as an important physiological defence process for photoprotection. Neutral luminal pH of melanosomes is critical for providing optimal conditions for the rate-limiting, pH-sensitive melanin synthesizing enzyme tyrosinase (TYR). As a major component of extraocular phototransduction pathway, transient receptor potential ankyrin1 (TRPA1) can be activated by ultraviolet B (UVB) and reported to be expressed in melanocytes. However, whether TRPA1 is involved in the regulation of melanogenesis remains unclear. Melanogenic activity of TRPA1 was evaluated in primary normal human epidermal melanocytes (HEMs) and murine B16-F10 cell cultures, and the effects of topical applications of TRPA1 specific agonist and antagonist on UVB-induced skin pigmentation were confirmed on in vivo guinea pig models. Calcium (Ca 2+ ) imaging and pH imaging were performed to analyse the effects of TRPA1 on intracellular Ca 2+ concentration ([Ca 2+ ] ic ) and melanosome luminal pH. TRPA1 regulated melanin synthesis, UVB-induced Ca 2+ influx and melanosome luminal pH in HEMs and B16-F10 cells. Topical treatment of TRPA1 specific agonist JT010 increased UVB-induced skin pigmentation in guinea pigs, while topical using of TRPA1 selective antagonist HC-030031 mitigated such pigmentation. Our results indicated that TRPA1 activated by UVB enhanced the skin pigmentation, most likely by regulating the [Ca 2+ ] ic and the melanosomal pH, consequently influencing the enzymatic activity of TYR. Therefore, the results suggest TRPA1 as a potential therapeutic target in the treatment of skin pigmented disorders that are at high risk under UVB irradiation.

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Section: Discussionmentioning

confidence: 99%

“…Hence, agreeing with our results, inhibition of TRPA1 seem to have a miner effect on the protein expression of gp100, but a major effect on melanin content. Additionally, in 2021, Jia et al 37 ] im and the biological responses in melanosomes. 39 In 2016, Ambrosio et al 30 proposed that knockout of the gene encoded twopore channel 2 (TPC2) protein, a cation release channel expressed in the melanosome-limiting membrane in human melanocytes, produced a decrease of the peri-melanosomes calcium concentration and an increase in melanosome luminal pH, eliciting a significant increase in melanin content and larger size of melanosomes.…”

Section: Topical Treatment With Trpa1 Specific Antagonist Hc-030031 M...mentioning

confidence: 99%

TRPA1 promotes UVB‐induced skin pigmentation by regulating melanosome luminal pH

Wang

Liu

et al. 2022

Experimental Dermatology

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“…A densitometric analysis of the pigmented dish was determined using the ImageJ software, as described previously for tadpoles [35]. Biochemical determination of melanin synthesis was performed as described previously [38]. Briefly, melanophores were harvested, and the number of cells quantified in a Neubauer counting chamber.…”

Section: Melanin Synthesis Assaymentioning

confidence: 99%

Interplay of Light, Melatonin, and Circadian Genes in Skin Pigmentation Regulation

Bertolesi,

Debnath,

Heshami

et al. 2024

Preprint

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Circadian regulation of skin pigmentation is essential for thermoregulation, UV protection, and synchronization of skin cell renewal. This regulation involves both cell-autonomous photic responses and non-cell-autonomous hormonal control, particularly through melatonin produced in a light-sensitive manner. Photosensitive opsins, cryptochromes, and melatonin regulate circadian rhythms in skin pigment cells. We studied light/dark cycles and melatonin coordination in melanin synthesis and cell proliferation of Xenopus laevis melanophores. In vivo, tadpole pigmentation shows robust circadian regulation mainly hormone-driven, in that isolated melanophores respond strongly to melatonin but only slightly to light. Melanophore proliferation is faster in the dark and slower with melatonin compared to a 12/12 light/dark cycle. Expression of circadian core genes (clock, bmal1, per1, per2, per3, cry1, cry2, and cry4) in melatonin-treated cells during the light phase mimics dark phase expression. Individual Cry overexpression did not affect melanisation or cell proliferation, likely due to functional redundancy. Melanin synthesis was inhibited by circadian cycle deregulation through: a) pharmacological inhibition of Cry1 and Cry2 degradation with KL001, b) continuous light or dark conditions, and c) melatonin treatment. Our findings suggest that circadian cycle regulation, rather than proliferative capacity, alters melanisation of melanophores.

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Roles of Intramolecular Interactions in the Regulation of TRP Channels

Cai

Chen

2022

Reviews of Physiology, Biochemistry and Pharmacology

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Transient Receptor Potential channels, TRPV1 and TRPA1 in melanocytes synergize UV‐dependent and UV‐independent melanogenesis

Cited by 8 publications

References 54 publications

TRPA1 promotes UVB‐induced skin pigmentation by regulating melanosome luminal pH

TRPA1 promotes UVB‐induced skin pigmentation by regulating melanosome luminal pH

Interplay of Light, Melatonin, and Circadian Genes in Skin Pigmentation Regulation

Roles of Intramolecular Interactions in the Regulation of TRP Channels

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