Hot on the Trail of Skin Inflammation: Focus on TRPV1/TRPV3 Channels in Psoriasis

Transient Receptor Potential Vanilloid (TRPV) channels are expressed in various skin cells, including non-neuronal cell types such as epidermal keratinocytes. They are polymodal sensors of the environment, regulating physiological function in response to a wide variety of stimuli. Indeed, in addition to their significant role in thermal responses and thermoregulation, TRPV channels are also implicated in local skin inflammation processes. Thus, these calcium permeable channels are associated to multiples skin diseases with inflammation, such as atopic dermatitis or psoriasis. In this chapter, we will mainly focus on TRPV1 and TRPV3 channels, as emerging pivotal targets for maintaining skin homeostasis in psoriasis-related inflammation

Vasodilatation cutanée induite par l application d une presse externe (implication des canaux potassiques)

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

L'effet du vieillissement sur la microcirculation cutanée

L'application d'une pression sur la peau provoque une vasodilatation cutanée, appelée vasodilatation induite par une pression (PIV), et retarde l'apparition de l'ischémie tissulaire liée à cette pression. La pression appliquée sur la peau active les fibres nerveuses capsaïno-sensibles, qui sécrètent en réponse des neurotransmetteurs, qui eux provoquent au niveau de l'endothélium la synthèse et la sécrétion de facteurs endothéliaux qui induisent une relaxation du muscle lisse. Ce travail avait pour objectif d'étudier l'effet du vieillissement sur la PIV. Chez la souris âgée, sans neuropathie périphérique, la PIV était altérée en raison d'une diminution de la vasodilatation endothélium-dépendante ; et la contribution des facteurs endothéliaux de la vasodilatation était modifiée : l'Endothelium-Derived Hyperpolarizing Factor jouait un rôle primordial en raison d'une diminution du monoxyde d'azote et de la prostacycline. Chez les sujets âgés (60-75 ans), la PIV était altérée en comparaison avec les sujets jeunes (20-35 ans) en raison d'une diminution de la vasodilatation endothélium-dépendante mais aussi d'une altération des fibres capsaïno-sensibles et/ou des neurotransmetteurs. En présence d'une neuropathie périphérique, la PIV était abolie. Ces modifications de la microcirculation cutanée au cours du vieillissement expliqueraient la plus grande vulnérabilité de la peau à l'ischémie et l'augmentation du risque d'ulcère de pression liée à l'âge. La compréhension des modifications de la PIV avec l'âge permet d'entrevoir de nouvelles perceptives de prévention et de traitement de l'ulcère de pression chez le sujet âgéThe pressure application on the skin leads to an increase of the cutaneous blood flow, called pressure-induced vasodilatation (PIV), that delays the occurrence of tissue ischemia resulting from this pressure. The development of this PIV depends on the activation by pressure of sensory C-fibres, leading to the release of neurotransmitters that acts at the endothelium level to stimulate the synthesis and release of endothelial factors inducing smooth muscle relaxation. This work had for objective to study the modifications of the PIV with the ageing. In old mice, without peripheral neuropathy, the PIV was reduced because of a decrease of the endothelium-dependent vasodilatation and the endothelium factors of the vasodilatation were redistributed with a contribution of Endothelium-Derived Hyperpolarizing Factor because of a decrease of the nitric oxide and the prostacyclin. In old subjects (60-75 years), the PIV was altered in comparison with young subjects (20-35 years) because of a decrease of the endothelium-dependent vasodilatation and a sensory fibres and/or neuromediators alteration. In the presence of a peripheral neuropathy, the PIV was abolished. These modifications of the cutaneous microcirculation with the ageing would lead to an early occurrence of ischemia related to an increased risk for pressure ulcers and the understanding of PIV modifications allow to glimpse of news perceptives of prevention and treatment of pressure ulcers in elderlyLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Étude de la microcirculation cutanée au cours du vieillissement

ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Endothelium microenvironment sensing leading to nitric oxide mediated vasodilation: A review of nervous and biomechanical signals

International audienceBlood vessels are continuously exposed to various stresses such as mechanical strains and neurosignals. Besides its role as a barrier between blood and other tissues, the endothelium is a highly important cell layer for the regulation of vascular tone. Indeed, depending on the signal perceived by endothelial cells, it can drive a vasoconstrictor or vasodilator signal. This review presents mechano-receptors and neuro-receptors (restricted to neuropeptides) leading to vessel relaxation via the production of nitric oxide. Finally, some pieces of evidence of a potential cross-talk between these two kinds of stimuli are discussed

New regime in the mechanical behavior of skin: strain-softening occurring before strain-hardening

We report linear and non-linear shear tests on rat skin, evidencing a strain-softening regime, from 1% to 50% strain, followed by a strong strain-hardening regime, leading to a ?deck chair-shaped? stress-strain curve. The strain-softening regime was never reported as such in the literature, possibly mistaken for the linear regime in experiments starting above 1% deformation. The time-dependent response is akin to that of a gel, with a power-law frequency-dependent dynamic shear modulus ranging from ~5.6 kPa to ~10 kPa between 0.1 Hz and 10 Hz. We present an analytical non-linear viscoelastic model that accounts for both time-dependent and strain-dependent features of the skin. This eight-parameter model extends the one we proposed for parenchymatous organs by including strain-softening

Vieillissement et intégrité de la peau

La peau est un organe sentinelle, soumis au vieillissement chronologique et environnemental qui fragilise sa structure et ses fonctions. La fonction barrière de la peau, ses propriétés élastiques et de résistance, ainsi que sa réactivité vasculaire sont atteintes par le vieillissement dans les compartiments épidermiques, dermiques et vasculaires. Les progrès de la recherche ont permis de révéler des processus biologiques sous-jacents, qui peuvent être ciblés par des approches médicamenteuses topiques ou globales à base notamment d’anti-oxydants ou de sénolytiques. Ces stratégies anti-âge pourront contribuer à restaurer, au moins en partie, l’intégrité fonctionnelle de la peau âgée

Sickle-cell trait and diagnosis of type 2 diabetes

International audienc

Asic3 is a neuronal mechanosensor for pressure-induced vasodilation that protects against pressure ulcers.

International audiencePressure-induced vasodilation (PIV) delays the decrease in cutaneous blood flow produced by local application of low pressure to the skin, a physiologically appropriate adjustment of local vasomotor function. Individuals without a normal PIV response have a high risk of ulceration. Here we demonstrate that acid-sensing ion channel 3 (Asic3) is an essential neuronal sensor for the vasodilation response to direct pressure in both humans and rodents and for protecting against pressure ulcers in mice