Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: role of cold‐sensitive TRP receptors in epidermal permeability barrier homoeostasis

Denda, Mitsuhiro; Tsutsumi, Moe; Denda, Sumiko

doi:10.1111/j.1600-0625.2010.01154.x

Cited by 68 publications

(46 citation statements)

References 26 publications

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“…The range of thermoactivation of TRPM8 channel fits well with human unprotected skin temperature, +24°C to +33°C (5, 6). Apart from the observation that topical application of TRPM8 chemical agonists can improve epidermal regeneration (16), no solid evidence for the expression of functional TRPM8 in epidermal keratinocytes has been presented yet and no alterations in epidermal homeostasis have been reported in trpm8 −/− null mutant mice suppressing the full-length TRPM8 cold receptor (17,18). However, suppression of the full-length TRPM8 expression does not necessarily affect expression of TRPM8 isoforms (19).…”

Section: •−mentioning

confidence: 99%

Epidermal TRPM8 channel isoform controls the balance between keratinocyte proliferation and differentiation in a cold-dependent manner

Bidaux

Borowiec

Gordienko

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Deviation of the ambient temperature is one of the most ubiquitous stimuli that continuously affect mammals' skin. Although the role of the warmth receptors in epidermal homeostasis (EH) was elucidated in recent years, the mystery of the keratinocyte mild-cold sensor remains unsolved. Here we report the cloning and characterization of a new functional epidermal isoform of the transient receptor potential M8 (TRPM8) mild-cold receptor, dubbed epidermal TRPM8 (eTRPM8), which is localized in the keratinocyte endoplasmic reticulum membrane and controls mitochondrial Ca 2+ concentration ([Ca 2+ ] m ). In turn, [Ca 2+ ] m modulates ATP and superoxide (O •−2 ) synthesis in a cold-dependent manner. We report that this fine tuning of ATP and O •−2 levels by cooling controls the balance between keratinocyte proliferation and differentiation. Finally, to ascertain eTRPM8's role in EH in vivo we developed a new functional knockout mouse strain by deleting the pore domain of TRPM8 and demonstrated that eTRPM8 knockout impairs adaptation of the epidermis to low temperatures.he skin epidermis provides a protective barrier that guards the body against an uncongenial environment. Under the influence of a variety of ambient factors the skin epidermis undergoes continuous regeneration through so-called epidermal homeostasis (EH): the fine-tuning of the balance between proliferation, directional migration, differentiation, and death of keratinocytes. EH involves complex molecular and chemical pathways, regulating dynamic and continuous transition of keratinocytes from the proliferating state in the basal layer to the nonproliferating state in the suprabasal layer before the beginning of the differentiation in the stratum spinosum and stratum granulosum. The terminal differentiation step, characterized by keratinocyte death, transforms keratinocytes into corneocytes, which form the waterproof, mechanically resistant sheath of the stratum corneum (1).Deviation of the ambient temperature is one of the most important stimuli that constantly affect mammals' skin. At ambient temperatures from +10°C to +30°C, the unprotected human skin temperature settles at mean steady-state values within the range of +24°C to +33°C, respectively (2). Temperature is perceived by thermoreceptors, the ion channels that belong to the transient receptor potential (TRP) superfamily (for review see ref.3). Of these, TRPV1 and TRPV2 are activated by heat (above 42°C and above 52°C, respectively) (4), whereas TRPM8 and likely TRPA1 are activated by mild (5, 6) and noxious (7-9) cold, respectively. Heatstimulated keratinocytes have been shown to secrete ATP (10) and, taking into account that purinergic receptors are expressed in keratinocytes (11), TRPV3 is involved in a paracrine heat-

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Section: •−mentioning

confidence: 99%

Epidermal TRPM8 channel isoform controls the balance between keratinocyte proliferation and differentiation in a cold-dependent manner

Bidaux

Borowiec

Gordienko

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…These results suggested that TRPA1 serves as a functional cold-sensitive calcium channel in human epidermal keratinocytes. We also established that TRPM8 was expressed in epidermal keratinocytes, by means of immunohistochemical study and RT-PCR [ 41 ] . Table 6.1 Effects of dry environment (low humidity) on skin pathophysiology Amplifi cation of hyperproliferative response to barrier disruption [ 28 ] Abnormal desquamation of the stratum corneum [ 93 ] Elevation of DNA synthesis in basal layer of the epidermis [ 92 ] Enhancement of barrier function [ 27 ] Appearance of abnormal skin surface morphology [ 94 ] Amplifi cation of allergic reaction [ 55 ] Elevation of IL-1 a mRNA and protein [ 4 ] Amplifi cation of proliferative response induced by surfactant [ 19 ] Decrease of water-holding capacity and free amino acid content in stratum corneum [ 67,94 ] Abrupt decrease in environmental humidity induces abnormalities in barrier homeostasis [ 95 ] Alteration of calcium distribution in epidermis [ 45 ] Increase of mast cell number and histamine content in dermis [ 3 ] Previously, we had found that calcium dynamics was associated with epidermal permeability barrier homeostasis [ 35 ] .…”

Section: Transient Receptor Potential (Trp) Familymentioning

confidence: 99%

Sensory Systems of Epidermal Keratinocytes

Denda

2012

Treatment of Dry Skin Syndrome

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“…ß-glucan receptors) present in the intercellular spaces, as shown for an endangerd epidermis like in the capybara (Meyer et al 2008), confirms again the view of a complex barrier biology (Elias 2007). Last but not least, the skin surface temperature may activate or block epidermal barrier homeostasis by temperature sensors (members of the transient receptor potential family), in particular, when the outer temperatures distinctly increase (Denda et al 2007) or decrease (Denda et al 2010). This influence is of some interest for species with no hair coat or with seasonally varying hair coat qualities, but not for otters with a constantly dense fur (Kuhn 2009).…”

Section: Discussionmentioning

confidence: 99%

Basic structural and functional characteristics of the epidermal barrier in wild mammals living in different habitats and climates

et al. 2011

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Based on the combination of standard light and transmission electron microscopy, cryo-SEM, immunohistochemistry and a new sensitive glycolipid histochemical technique (5-hexadecanoylaminofluorescein staining, laser scanning microscopy), including densitometrical evaluation, our approach gives for the first time an overview of the specific biology of the epidermal permeability barrier in wild mammals (20 species from five orders), living under varying (aquatic or moist to dry) habitat conditions. The results obtained emphasised that the barrier region in most of the species studied is a continuous zone (thickness, 0.1 and 3 μm) between the upper cells of the stratum granulosum and the inner cells of the stratum corneum conjunctum, normally present as a homogeneous glycolipid layer originating from fusion of lamellar body contents after exocytotic activities of the granular cells. However, this finding did not apply to all of the species studied, i.e., the Wild boar, the Common seal and the three large species with a very thick vital epidermis, the African elephant, the hippopotamus and the common dolphin, exhibited variations from the basic scheme. Densitometric evaluation of the 5-hexadecanoylaminofluorescein staining revealed that reaction intensity was not only generally related to the habitat conditions but also to vital epidermis thickness and hair density. The immunohistochemical demonstration of Na + /H + exchanger 1 corroborated for all wild mammals studied that this important regulator of pH conditions during barrier formation is continuously produced in the epidermis. The variations in barrier biology observed for some species obviously had to be developed in relation to animal size (or body size area) and hair coat density, but, particularly, by the specific adaptation of certain mammalian groups to the aquatic environment. In the latter case, the typical barrier zone system was lost, as in the hippopotamus or the cetaceans.

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Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: role of cold‐sensitive TRP receptors in epidermal permeability barrier homoeostasis

Cited by 68 publications

References 26 publications

Epidermal TRPM8 channel isoform controls the balance between keratinocyte proliferation and differentiation in a cold-dependent manner

Epidermal TRPM8 channel isoform controls the balance between keratinocyte proliferation and differentiation in a cold-dependent manner

Sensory Systems of Epidermal Keratinocytes

Basic structural and functional characteristics of the epidermal barrier in wild mammals living in different habitats and climates

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