Modulation of Piezo1 influences human skin architecture and oxytocin expression.

OBJECTIVE: Throughout our existence, the skin senses and analyses the mechanical forces imposed by the environment. In response to these environmental forces, skin can deform itself and achieve a biological response. The subsequent cutaneous plasticity emerges from mechanical properties arising from the collective action of the skin cells, particularly keratinocytes, that govern the tensile strength via cell-to-cell adhesions and via cell-matrix adhesion structures. In addition to serving as force-bearing entities, keratinocytes respond to forces by activating signalling pathways to control their own fate and function. To detect and adapt to mechanical signals, keratinocytes possess a panel of sensory receptors and junctional intercellular structures. Mechanically activated ion channel Piezo1 has been described as a force sensor and as being involved in pleasant touch perception. In this study, relationships between Piezo1 modulation and oxytocin synthesis were investigated. METHODS: The expression of Piezo1 in the skin was studied and compared with the expression of TRPV1. Dooku1 antagonist and Jedi1 agonist were used to modulate Piezo1. The level of E-cadherin and oxytocin was monitored in ex vivo skin biopsies by immunodetection. RESULTS: Taken together, our results illustrate the major role of mechanosensitive ion channel Piezo1 in skin barrier integrity, and in peripheral oxytocin synthesis in the skin. CONCLUSION: In conclusion, this study highlights the relationships between pleasant touch, soft touch and local oxytocin synthesis.

OBJECTIF: Tout au long de notre existence, la peau détecte et analyse les forces mécaniques imposées par l'environnement. En réponse à ces forces environnementales, la peau peut se déformer et obtenir une réponse biologique. La plasticité cutanée qui s'ensuit émerge des propriétés mécaniques découlant de l'action collective des cellules cutanées, en particulier les kératinocytes, qui déterminent la résistance à la traction via les adhérences intercellulaires et les structures d'adhésion cellule-matrice. En plus de servir d'entités porteuses de force, les kératinocytes répondent aux forces en activant les voies de signalisation pour contrôler leur propre destin et leur propre fonction. Pour détecter et s'adapter aux signaux mécaniques, les kératinocytes possèdent un panel de récepteurs sensoriels et de structures intercellulaires jonctionnelles. Le canal ionique activé mécaniquement Piezo1 a été décrit comme un capteur de force et comme étant impliqué dans la perception d'un toucher agréable. Dans cette étude, les relations entre la modulation Piezo1 et la synthèse de l'ocytocine ont été étudiées. MÉTHODES: L'expression de Piezo1 dans la peau a été étudiée et comparée à l'expression de TRPV1. L'antagoniste Dooku1 et l'agoniste Jedi1 ont été utilisés pour moduler Piezo1. Le taux de cadhérine-E et d'ocytocine a été contrôlé dans des biopsies cutanées ex vivo par immunodétection. RÉSULTATS: Dans l'ensemble, nos résultats illustrent le rôle majeur du canal ionique mécanosensible Piezo1 dans l'intégrité de la barrière cutanée et dans la synthèse de l'ocytocine périphérique dans la peau. CONCLUSION: En conclusion, cette étude met en évidence les relations entre le toucher agréable, le toucher doux et la synthèse d'ocytocine locale.

Soothing Effect of Pogostemon cablin Extract (Patchouli), via Cannabinoid Receptor 2 Modulation in Human Skin.

Skin functions as a neuro-immuno-endocrine tissue with well-defined neuronal networks and functions. The endocannabinoid system has been proven to be an important, homeostatic regulator for homeostatic and inflammatory events. The system comprises endogenous or exogenous ligands and receptors (CB1 and CB2). In the present study, we evaluated the soothing properties of a Pogostemon cablin (patchouli) extract. Agonist AM1241 and antagonist AM630 were used for CB2 receptor activation/inhibition. Expression of CB2 receptor and ß-endorphin was monitored by immunohistochemistry. Skin inflammation was induced with ultraviolet B (UVB) or lipopolysaccharide (LPS), and the following markers were used to highlight the anti-inflammatory properties of the extract: transient receptor potential vanilloid 1 (TRPV1), interleukin receptors 1 (IL1R1), and the interleukin 6 signal transducer (IL6ST). Our results demonstrated the implication of the CB2 receptor in the skin inflammation process. The expression of CB2 receptor and ß-endorphin was increased 48 hours after application of the extract. Furthermore, patchouli extract application helped to reduce IL1R1, IL6ST, and TRPV1 expression, in skin exposed to UVB or LPS. In conclusion, the application of the patchouli extract helps maintain skin integrity and reduce skin discomfort via modulation of CB2 receptor stimulation and the subsequent ß-endorphin release.

High dietary lipids induce liver glucose-6-phosphatase expression in rainbow trout (Oncorhynchus mykiss).

To contribute to the understanding of the mechanisms involved in poor metabolic utilization of dietary carbohydrates by rainbow trout (Oncorhynchus mykiss), we explored in this study the effects of dietary lipids on the regulation of two hepatic key enzymes, i.e., glucokinase (GK, first enzyme of the glycolytic pathway) and glucose-6-phosphatase (G6Pase, last enzyme of the gluconeogenesis). Two groups of juvenile trout were pair-fed for 8 wk either a low (10%) or a high (25%) level of dietary lipids supplied as fish oil; the pair-feeding technique was adopted to vary fat intake while keeping the protein and carbohydrate intakes more or less constant. Fish fed the high level of dietary lipids had inefficient control of glycemia compared with fish fed the low level of lipids. Levels of dietary lipids did not affect GK activity even though there was a small increase of GK mRNA level at 3 h after feeding high levels of lipids. By contrast, the high level of dietary lipids significantly increased G6Pase mRNA expression at 3, 6 and 12 h and enzyme activity at 6 h after food consumption. Thus, these data suggest that poor dietary carbohydrate utilization in rainbow trout may be related at least in part to increased hepatic glucose production under conditions of high dietary fat intake.