Olfactory receptor OR2AT4 regulates human hair growth

Chéret, Jérémy; Bertolini, Marta; Ponce, L.; Lehmann, Janin; Tsai, Teresa; Alam, Majid; Hatt, Hanns; Paus, Ralf

doi:10.1038/s41467-018-05973-0

Cited by 102 publications

(138 citation statements)

References 66 publications

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“…OR2AT4 was later found to be expressed in the outer root sheath of hair follicles. Stimulation of OR2AT4 by sandalore suppressed apoptosis and extended hair growth and longevity [63], which suggests another possible use of OR2AT4, i.e., in avoiding thinning of hair. [64].…”

Section: The Skinmentioning

confidence: 95%

The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application

Koyama

Heinbockel

2020

IJMS

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Essential oils have been used in multiple ways, i.e., inhaling, topically applying on the skin, and drinking. Thus, there are three major routes of intake or application involved: the olfactory system, the skin, and the gastro-intestinal system. Understanding these routes is important for clarifying the mechanisms of action of essential oils. Here we summarize the three systems involved, and the effects of essential oils and their constituents at the cellular and systems level. Many factors affect the rate of uptake of each chemical constituent included in essential oils. It is important to determine how much of each constituent is included in an essential oil and to use single chemical compounds to precisely test their effects. Studies have shown synergistic influences of the constituents, which affect the mechanisms of action of the essential oil constituents. For the skin and digestive system, the chemical components of essential oils can directly activate gamma aminobutyric acid (GABA) receptors and transient receptor potential channels (TRP) channels, whereas in the olfactory system, chemical components activate olfactory receptors. Here, GABA receptors and TRP channels could play a role, mostly when the signals are transferred to the olfactory bulb and the brain.

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Section: The Skinmentioning

confidence: 95%

The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application

Koyama

Heinbockel

2020

IJMS

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“…For this purpose, it is essential to have reliable models for the examination of the effects of PPAR‐γ modulators specifically in the HF. One such instructive model is the human healthy or lesional HF or scalp skin organ culture that allows examination of many HF parameters (eg, hair growth, pigmentation, hair cycle, mitochondria, stem cells) simultaneously and in a reproducible manner, as was already shown with PPAR‐γ modulators . Nevertheless, HF organ culture has several limitations (eg, lack of innervation and endocrine effects, inter‐ and intra‐individual differences of harvested HFs, short anagen time), the most prominent one being the inability to test the complete HF cycle .…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Ramot

Bertolini

Boboljova

et al. 2019

Experimental Dermatology

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Peroxisome proliferator‐activated receptors (PPARs) are abundantly expressed in human skin, with PPAR‐γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR‐γ‐mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR‐γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR‐γ‐mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR‐γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial‐mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR‐γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.

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“…Ki‐67/TUNEL double‐immunofluorescence microscopy was performed on cryosections fixed in paraformaldehyde and ethanol–acetic acid (2:1) and labelled with a digoxigenin‐deoxyUTP (ApopTag Fluorescein In Situ Apoptosis Detection Kit) together with terminal deoxynucleotidyl transferase (TdT), followed by incubation with a mouse anti‐Ki‐67 antiserum (1:20, Dako, cat n. M7240) . Rhodamine‐labelled goat anti‐mouse antibody (Jackson ImmunoResearch) was used to detect Ki‐67.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, we assessed in situ epidermal keratinocyte apoptosis and proliferation by Ki‐67/TUNEL immunostaining , and epidermal progenitor cell numbers by immunostaining for the stem cell marker keratin 15 (K15) . ECM stability in situ was evaluated by immunostaining for collagen I and III and fibrillin‐1 , mitochondrial activity was examined by staining for MTCO1, and the ageing phenotype by sirtuin‐1 .…”

Section: Introductionmentioning

confidence: 99%

Theophylline exerts complex anti‐ageing and anti‐cytotoxicity effects in human skin ex vivo

Bertolini

Ramot

Gherardini

et al. 2019

Intern J of Cosmetic Sci

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OBJECTIVE: Theophylline is a phosphodiesterase inhibitor that is being used clinically for asthma therapy. In addition, it is recognized as a cosmetic agent with possible anti-ageing and anti-oxidative properties. Nevertheless, how it affects human skin is still poorly examined. METHODS: Theophylline (10 or 100 µM) was administered to the culture medium of full-thickness human skin ex vivo for 24 or 72 h. RESULTS: Theophylline stimulated protein expression of the antioxidant metallothionein-1 and mRNA levels of collagen I and III. Assessment of fibrillin-1 immunohistology revealed enhanced structural stability of dermal microfibrils. Theophylline also exerted extracellular matrix-protective effects by decreasing MMP-2 and MMP-9 mRNA levels, partially antagonizing the effects of menadione, the potent, toxic ROS donor. In addition, it decreased menadione-stimulated epidermal keratinocytes apoptosis. Interestingly, theophylline also increased the level of intracutaneously produced melatonin, that is the most potent ROS-protective and DNA damage repair neuromediator, and tendentially increased protein expression of MT1, the melatonin receptor. Theophylline also increased the expression of keratin 15, the stem cell marker, in the epidermal basal layer but did not change mitochondrial activity or epidermal pigmentation. CONCLUSION: This ex vivo pilot study in human skin shows that theophylline possesses several interesting complex skin-protective properties. It encourages further examination of theophylline as a topical candidate for anti-ageing treatment. R esum e OBJECTIF: la th eophylline est un inhibiteur de la phosphodiest erase actuellement utilis ee en clinique pour le traitement de l'asthme. En outre, elle est reconnue comme etant un agent cosm etique ayant des propri et es potentiellement anti-âge et antioxydantes. Cependant, la mani ere dont elle affecte la peau chez l'homme est encore tr es peu etudi ee. M ETHODES: de la th eophylline (10 ou 100 lM) a et e ajout ee dans le milieu de culture d'un echantillon de peau humaine d' epaisseur totale ex vivo pendant 24 ou 72 h. Theophylline effects in human skin ex vivo M. Bertolini et al. 84 Theophylline effects in human skin ex vivo M. Bertolini et al. Theophylline effects in human skin ex vivo M. Bertolini et al. Theophylline effects in human skin ex vivo M. Bertolini et al.

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Olfactory receptor OR2AT4 regulates human hair growth

Cited by 102 publications

References 66 publications

The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application

The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Theophylline exerts complex anti‐ageing and anti‐cytotoxicity effects in human skin ex vivo

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