Accueil du site > Equipes > Fonctionnalité et dynamique du tissu cutané (D. Sigaudo-Roussel) > Thématiques > Propriétés mécaniques du tissu cutané > Mechanical properties of cutaneous tissues
Project leader : B. Fromy
Persons involved in the project : J. Decorps, L. Moulin, P. Sommer, C. Mainzer, C. Loirond, G Annivo, J. Vial, A. Josset-Lamaugarny, G. Aimond, D. Benzoni, D. Sigaudo-Roussel, J.L. Saumet
Skin fragility during aging
Specific biological processes allow healthy skin to withstand the mechanical stresses, especially with the ability to vasodilation of microvessels of the skin to increase skin blood flow when light pressure is applied. This vasodilation is called PIV for pressure-induced vasodilation. Older people are deprived of this physiologically appropriate adjustment of local vasomotor function (PIV) and have an early decline in skin blood flow in response to very low pressures, indicating skin fragility during aging that could partly explain the high risk for pressure ulcers in elders.
Although the processes are not clearly understood, vascular aging is largely associated with increased oxidative stress and its consequences. The vascular endothelium appears to be an important source of free radical species (ROS reactive oxygen species) including superoxide anion, causing attenuation of endothelium-dependent relaxations and stiffening of the elastic walls, which may be limited by antioxidant treatments. Thus, changes in the synthesis and bioavailability of nitric oxide (NO) prevalent to explain the endothelial dysfunction.
The importance of oxidative stress has also been proposed in diabetes for many years. We showed the preventive effect of alpha-lipoic acid (daily treatment for a week) in diabetic mice and demonstrated that chronic antioxidant treatment appears promising for a preventive approach against pressure ulcer. This preventive approach regarding pressure ulcers is totally novel and is supported by the CNRS (AAP CNRS), the Rhône-Alpes Region (ARC2) and PERSE association.
Parallel to the study of dermis aging (via the loss or modification of the elastic fibers, particularly in the dermal-epidermal junction), we focus on the aging of the epidermis, including the enzymes involved in the formation of collagen and elastic fibers. Previously, the importance of lysyl oxidase (LOX) in the formation of the epidermis has been demonstrated. Its absence causes defective keratinocyte differentiation and formation of the epidermis. We focus on the study of regulation by IGF1, known for its positive effect on wound healing and UV protection, but also for the regulation of elastogenesis.
The study will include the in vitro model of aging on reconstructed epidermis and identification of cellular markers of aging generated by oxidative stress in low hormonal pressure (to mimic aging), especially in terms of potential proliferation-differentiation of keratinocytes. This program is supported by the company Natura (2009-2014).
Identification of cellular signaling pathways involved in microvascular adjustments
Many cutaneous receptors exist in the skin, as well as more complex structures to receive and translate the information of the stimulus into an electrical signal. These receptors include mechanoreceptors, thermoreceptors and nociceptors found in the superficial and deep layers of the skin. The vasomotor skin reactions in response to a non-nociceptive mechanical stress had almost never been studied.
The team demonstrated the presence of vasodilation in response to the application of a low pressure called PIV for "pressure-induced vasodilation." This vasodilation 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 to protect the skin against pressure-induced lesions. Individuals without a normal PIV response have a high risk of ulceration.
As the starting point of the PIV is the detection of mechanical stimulus on the skin, channels / mechanosensitive receptors retain our attention. The involvement of different mechanoreceptors in the neurovascular response (PIV) in the skin are studied experimentally (pharmacological approach, transgenic animals) and clinically.
In connection with the work on the elastogenesis, we aim to determine whether the elastic properties of the skin change the protective properties of human skin against mechanical stress, through PIV modulation. Early studies indicate that moderate enzymatic degradation of elastic fibers affects the PIV, without changes in tissue organization. This study will be developed by studying the level at which the elastic deficit can affect the PIV (dermal environment, vascular, nervous ...).
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