The human skin is a sensory organ, sensations from our environment are gathered by nerve fibers. Cutaneous fibers are classified as Aβ, Aδ and C-fibers based on their diameter, myelinization, and velocity of conduction. Nerve fibers are found in the dermis and, as free nerve endings in the epidermis. Low threshold mechanosensitive C-fibers convoy affective touch. Touch and proprioception involve piezo1 and piezo2 mechanoreceptors. Piezo1 was described in keratinocyte, a localization that could help modulate mechanoperception. Piezo2 is the main mechanotransducer found in C-type fibers, and patients with piezo2 null variant mutations show deficits in touch perception and proprioception.
We developed a new cellular model of cultured neurons with C-type fibers characteristics. This model was characterized and showed the expression of specific markers. In this study, we investigated the role of piezo1 in skin barrier function, and the relationship with the oxytocinergic pathway. In the skin, the oxytocinergic system declines with age and is associated with barrier function impairment. We have screened various plant extract for their ability to modulate both piezo mechanotransducer and the ocytocinergic patway.
Our results showed that piezo1 expression in the epidermis decreased with age. Moreover, inhibition of piezo1 in ex vivo skin, by a selective antagonist, significantly compromised the integrity of cellular junctions, and the skin peripheric oxytocinergic pathway. The application of a botanical extract was observed to preserve piezo1 expression, the local synthesis of oxytocin, and the expression of its receptor OXTR. Finally, application of the botanical extract on keratinocytes, was associated with an increase of innate immune function.
These results highlighted the importance of maintaining piezo receptors in skin, to preserve the mechanical communication between cells and their environment. In this work, we provide knowledge on existing bond between mechanosensation and the neuroendocrine–immune network.