TRPV4 Is Expressed in Human Hair Follicles and Inhibits Hair Growth In Vitro

Szabó, Imre; Herczeg-Lisztes, Erika; Szegedi, Andrea; Nemes, Balázs; Paus, Ralf; Bı́ró, Tamás; Szöllősi, Attila Gábor

doi:10.1016/j.jid.2018.11.020

Cited by 20 publications

(19 citation statements)

References 16 publications

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“…One explanation for this discrepancy might be that the cellular toxicity produced by the constitutive channel activity of the gain‐of‐function TRPV3 mutation causes death of hair follicle keratinocytes as gain‐of‐function TRPV3 mutations induced marked cell death in vitro (Lin et al, 2012; Xiao, Tian, Tang, & Zhu, 2008). In marked contrast to a recent study showing that TRPV4 activation by GSK1016790A decreased the ratio of proliferating cells and increased the number of apoptotic cells in cultured human hair follicles ex vivo and presumably resulted in an inhibition of hair growth (Szabo et al, 2019), our results showed that transient stimulation of the TRPV4‐expressing hair follicle keratinocytes by a small molecule activator promoted hair follicle regeneration in vivo in mice. The discrepancy in these two studies might be caused by species differences in TRPV4 function in hair follicles between mice and humans as well as differences in experimental settings in which our studies examined hair follicle regeneration in vivo, while Szabó et al evaluated anagen maintenance ex vivo using cultured human hair follicles.…”

Section: Discussioncontrasting

confidence: 99%

“…Our previous study further demonstrated that TRPV4 is highly expressed by both skin keratinocytes and dermal macrophages and contributes to the pathogenesis of both allergic and non‐allergic chronic itch in mice (Luo et al, 2018). Although a recent study showed that activation of TRPV4 induces apoptosis and drives early catagen transition in human hair follicles, which inhibits human hair growth ex vivo (Szabo et al, 2019), the role of TRPV4 in hair follicle regeneration in vivo remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Transient stimulation of TRPV4‐expressing keratinocytes promotes hair follicle regeneration in mice

Lü

Luo

et al. 2020

British J Pharmacology

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Background and Purpose: Hair follicle telogen to anagen transition results in a break in cellular quiescence of the hair follicle stem cells, which subsequently promotes hair follicle regeneration. Many critical molecules and signalling pathways are involved in hair follicle cycle progression. Transient receptor potential vanilloid 4 (TRPV4) is a polymodal sensory transducer that regulates various cutaneous functions under both normal and disease conditions. However, the role of TRPV4 in hair follicle regeneration in vivo remains incompletely understood. Experimental Approach: Using adult C57BL/6J mice, keratinocyte (K14 Cre ; Trpv4 f/f) and macrophage (Cx3cr1 Cre ; Trpv4 f/f) Trpv4 conditional knockout (cKO) mice, Trpv4 −/− mice, we investigated the effect of a single intradermal injection of GSK1016790A, a potent and selective small molecule TRPV4 activator, on hair follicle regeneration. Chemical cues and signal molecules involved in hair follicle cycle progression were measured by immunofluorescence staining, quantitative RT-PCR and western blotting. Key Results: Here, we show that a single intradermal injection of GSK1016790A is sufficient to induce telogen to anagen transition and hair follicle regeneration in mice by increasing the expression of the anagen-promoting growth factors and downregulating the expression of growth factors that inhibit anagen. The action of GSK1016790A relies largely on the function of TRPV4 in skin and involves activation of downstream ERK signalling. Conclusion and Implications: Our results suggest that transient chemical activation of TRPV4 in the skin induces hair follicle regeneration in mice, which might provide an effective therapeutic strategy for the treatment of hair loss and alopecia. 1 | INTRODUCTION The hair follicle is the most prominent mini-organ found in the skin. It is composed of three main components: the outer root sheath, the inner root sheath and the hair shaft. The hair follicle cyclically transforms from rapid growth (anagen), to apoptosis-driven regression (catagen) and last to relative quiescence (telogen) phases (Muller-Rover et al., 2001; Oshima, Rochat, Kedzia, Kobayashi, & Barrandon, 2001). Many critical molecules and signalling pathways are involved in these distinct phases of hair follicle cycle progression. The quiescence of hair follicle stem cells during telogen is largely maintained by bone morphogenetic proteins (BMPs) derived

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transient stimulation of TRPV4‐expressing keratinocytes promotes hair follicle regeneration in mice

Lü

Luo

et al. 2020

British J Pharmacology

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“…TRPV3 and TRPV4 were also detected in human hair follicles and outer root sheath keratinocytes, and receptor activation, though not exclusively by cannabinoids, resulted in suppression of hair follicle elongation. 115 , 116 A metabolite of the endocannabinoid anandamide, bimatoprost, is recognized as a topical prostamide treatment for eyebrow hypotrichosis. 117 Khidhir et al also showed human scalp hair follicles possess select prostamide receptors within the dermal papilla.…”

Section: Introductionmentioning

confidence: 99%

<p>Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders</p>

Baswan¹,

Klosner²,

Glynn³

et al. 2020

CCID

123

113

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Though there is limited research confirming the purported topical benefits of cannabinoids, it is certain that cutaneous biology is modulated by the human endocannabinoid system (ECS). Receptors from the ECS have been identified in the skin and systemic abuse of synthetic cannabinoids, and their analogs, have also been associated with the manifestation of dermatological disorders, indicating the effects of the ECS on cutaneous biology. In particular, cannabidiol (CBD), a non-psychoactive compound from the cannabis plant, has garnered significant attention in recent years for its anecdotal therapeutic potential for various pathologies, including skin and cosmetic disorders. Though a body of preclinical evidence suggests topical application of CBD may be efficacious for some skin disorders, such as eczema, psoriasis, pruritis, and inflammatory conditions, confirmed clinical efficacy and elucidation of underlying molecular mechanisms have yet to be fully identified. This article provides an update on the advances in CBD research to date and the potential areas of future exploration.

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“…Besides CB 1 , several cannabinoid-responsive TRPV channels (namely TRPV1, TRPV3 and TRPV4) were shown to be functionally expressed in human HFs, and to promote the onset of catagen phase [135,136,137,138], which, considering that all three channels are heat-sensitive [45,94,95,139], may be an evolutionary relic of warmth-induced shedding. Last, but not least, preliminary evidence suggests that CBD may concentration-dependently promote (0.1 μM) or suppress (10 μM) hair shaft elongation, most likely in adenosine receptor and TRPV4-dependent manners, respectively [140].…”

Section: Translational Potential Of the Cutaneous Cannabinoid Signmentioning

confidence: 99%

Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System

et al. 2019

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The endocannabinoid system (ECS) has lately been proven to be an important, multifaceted homeostatic regulator, which influences a wide-variety of physiological processes all over the body. Its members, the endocannabinoids (eCBs; e.g., anandamide), the eCB-responsive receptors (e.g., CB1, CB2), as well as the complex enzyme and transporter apparatus involved in the metabolism of the ligands were shown to be expressed in several tissues, including the skin. Although the best studied functions over the ECS are related to the central nervous system and to immune processes, experimental efforts over the last two decades have unambiguously confirmed that cutaneous cannabinoid (“c[ut]annabinoid”) signaling is deeply involved in the maintenance of skin homeostasis, barrier formation and regeneration, and its dysregulation was implicated to contribute to several highly prevalent diseases and disorders, e.g., atopic dermatitis, psoriasis, scleroderma, acne, hair growth and pigmentation disorders, keratin diseases, various tumors, and itch. The current review aims to give an overview of the available skin-relevant endo- and phytocannabinoid literature with a special emphasis on the putative translational potential, and to highlight promising future research directions as well as existing challenges.

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TRPV4 Is Expressed in Human Hair Follicles and Inhibits Hair Growth In Vitro

Cited by 20 publications

References 16 publications

Transient stimulation of TRPV4‐expressing keratinocytes promotes hair follicle regeneration in mice

Transient stimulation of TRPV4‐expressing keratinocytes promotes hair follicle regeneration in mice

<p>Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders</p>

Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System

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