TRP channels in the skin

Abstract

Emerging evidence suggests that transient receptor potential (TRP) ion channels not only act as 'polymodal cellular sensors' on sensory neurons but are also functionally expressed by a multitude of non-neuronal cell types. This is especially true in the skin, one of the largest organs of the body, where they appear to be critically involved in regulating various cutaneous functions both under physiological and pathophysiological conditions. In this review, we focus on introducing the roles of several cutaneous TRP channels in the regulation of the skin barrier, skin cell proliferation and differentiation, and immune functions. Moreover, we also describe the putative involvement of several TRP channels in the development of certain skin diseases and identify future TRP channel-targeted therapeutic opportunities. LINKED ARTICLESThis article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-10 Abbreviations 5-HT, 5-hydroxytryptamine (serotonin); AD, atopic dermatitis; AHA, α-hydroxyl acid; ATP, adenosine 5'-triphosphate; BCC, basal cell carcinoma; BTCT, N-(4-t-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; CGRP, calcitonin gene-related peptide; DAR, Darier's disease; HF, hair follicle; IL, interleukin; KO, knockout; NO, nitrogen monoxide; ORS, outer root sheath; OS, Olmstead syndrome; PGE2, prostaglandine E2; SERCA, sarco/endoplasmic reticulum Ca 2+ -ATPase; SP, substance P; SSC, squamous cell carcinoma; TCA, trichloroacetic acid; TE, tumour-enriched; TGFβ2, transforming growth factor β2; TRP, transient receptor potential; TRPA, transient receptor potential ankyrin; TRPC, transient receptor potential cannonical; TRPM, transient receptor potential melastatin; WS12, (1R*,2S*)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamideThe skin is one of the largest organs of the human body; therefore, it exhibits a plethora of physiological and homeostatic regulatory mechanisms (see reviewed in Bukowskiy, 2009;Draelos and Pugliese, 2011;Oláh et al., 2012). Indeed, the skin (i) establishes and maintains the first line defence of the organism against various forms of physical, chemical, and biological harmful stimuli and challenges (barrier functions); (ii) is a highly active neuro-immuno-endocrine organ (actually, the skin and the nervous system have the same embryological origin; see Makrantonaki et al., 2010) as: the skin-localized sensory afferents are involved in the neuronal processing of multiple sensory modalities (e.g. pain, itch, touch, thermosensation); it functionally expresses all major humoral and cellular components of the innate and adaptive immunity ('skin immune system'); it is not only the target but also the source of several hormonal systems (e.g. vitamin D family, hypothalamic-pituitaryadrenal and hypothalamic-pituitary -thyroid axis hormones; Zouboulis, 2004;2009b); (iii) also maintains proper motor (e.g. piloerection, vasoregulation), exocrine (e.g. sw...

Antipruritic Effect of Natural Coumarin Osthole through Selective Inhibition of Thermosensitive TRPV3 Channel in the Skin

“…Although itch sensation has been studied at the spinal level (Sun and Chen, 2007;Sun et al, 2009;Mishra and Hoon, 2013) and at the central neural circuit through the spinoparabrachial pathway, which was recently identified to be activated during itch processing (Mu et al, 2017), the molecular targets critical for itch sensation at the peripheral skin level still remain largely unclear. Emerging evidence suggests that thermosensitive TRP channels (e.g., TRPV1, TRPV3, TRPV4, TRPA1) not only act as "cellular sensors" on sensory neurons but also are functionally expressed in non-neuronal cells, such as the keratinocytes of the skin (Tóth et al, 2014). Both TRPV1 and TRPA1 channels are expressed in nerve endings of cutaneous sensory afferent fibers involved in itch and pain sensation (Caterina and Pang, 2016).…”

Infundibular protein and RNA microarray analyses from affected and clinically non‐affected scalp in male androgenetic alopecia patients

“…[11] Three AGA-downregulated ion channel markers (LRRC26, KCNK5, and B3GNT3) detected, to date, have not been described in hair follicles.…”

“…In line with the postulated mode of action of minoxidil, one of the most successful therapeutic molecules for AGA, [10] we identified differentially regulated genes responsible for structure and function of cation channels. [11] Three AGA-downregulated ion channel markers (LRRC26, KCNK5, and B3GNT3) detected, to date, have not been described in hair follicles.…”

Sensitive Skin Syndromes and Transient Receptors Potential (TRP) Channels in Sensitive Skin

“…TRPV 4 is activated by heat, mechanical, hyperosmotic and stress. TRPM 8 is activated by cold, menthol, wasabi and mustard and while TRPA 1 is activated by cold, wasabi, mustard, horseradish and bradykinin [23][24][25][26][27].…”