Calcium Channels: Noteworthy Regulators and Therapeutic Targets in Dermatological Diseases.

Min Wang,Yaoxiang Sun,Ocansey Dkw,Peipei Wu,Linli Li,Hui Shi

doi:10.3389/fphar.2021.702264

Min Wang, Yaoxiang Sun + Show 4 more

Open Access

https://doi.org/10.3389/fphar.2021.702264

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Abstract

Dysfunctional skin barrier and impaired skin homeostasis may lead to or aggravate a series of dermatologic diseases. A large variety of biological events and bioactive molecules are involved in the process of skin wound healing and functional recovery. Calcium ions (Ca2+) released from intracellular stores as well as influx through plasma membrane are essential to skin function. Growing evidence suggests that calcium influx is mainly regulated by calcium-sensing receptors and channels, including voltage-gated, transient potential receptor, store-operated, and receptor-operated calcium channels, which not only maintain cellular Ca2+ homeostasis, but also participate in cell proliferation and skin cell homeostasis through Ca2+-sensitive proteins such as calmodulin (CaM). Furthermore, distinct types of Ca2+ channels not merely work separately, they may work concertedly to regulate cell function. In this review, we discussed different calcium-sensing receptors and channels, including voltage-gated, transient receptor potential, store-operated, and receptor-operated calcium channels, particularly focusing on their regulatory functions and inherent interactions as well as calcium channels-related reagents and drugs, which is expected to bridge basic research and clinical applications in dermatologic diseases.

Highlights

The skin is the largest and heaviest organ of the body and is subjected to a wide spectrum of traumatic injury
STIM2gated ORAI1 Ca2+ channels may regulate melanoma, because Stanisz et al (2014) demonstrated that ORAI1 and STIM2 are highly expressed and control store-operated Ca2+ entry in human melanoma, with silencing of ORAI1 and/or STIM2 inhibiting the ability of proliferation, invasion, and migration of melanoma cells. - These findings indicate that ORAI1 and STIM1/STIM2 are potentially useful therapeutic targets for preventing tumor metastasis
The expression of TRPV1 and TRPA1 is reported to be upregulated in epithelial cells of an alkali-burned cornea, and the absence of the TRPV1 and TRPA1 genes suppresses post-alkali burn inflammation and facilitates the final healing (Okada et al, 2011; Okada et al, 2014). These results suggest that TRPV1 and TRPA1 play a negative role in burn wound healing, TRPV1/TRPM3/TRPA1 triple knockout mice lack the acute withdrawal response to noxious heat that is necessary to avoid burn injury (Vandewauw et al, 2018)

Summary

Introduction

The skin is the largest and heaviest organ of the body and is subjected to a wide spectrum of traumatic injury. In non-excitable cells, TRP channels regulate intracellular calcium concentrations, which are related to keratinocytes proliferation and differentiation to influence skin barrier (Moran et al, 2018). TRPCs are nonselective cation channels that are expressed in both excitable and non-excitable cells and regulate intracellular Ca2+ influx in response to numerous physiological or pathological stimuli (Feng, 2017).

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