Abstract
The skin has many functions, such as providing a barrier against injury and pathogens, protecting from ultraviolet light, and regulating body temperature. Mechanical causes and many different pathologies can lead to skin damage. Therefore, it is important for the skin to be always adaptable and renewable and for cells to undergo proliferation. Here, we demonstrate that 1α, 25-dihydroxyvitamin D3 (VD3) stimulates keratinocyte proliferation, leading to wound closure in a simulation model of injury. Functionally, our results show that VD3 acts by stimulating cyclin D1, a cyclin that promotes the G1/S transition of the cell cycle. The study on the mechanism underlying cyclin D1 expression upon VD3 stimulation clearly demonstrates a key role of neutral sphingomyelinase. The enzyme, whose gene and protein expression is stimulated by VD3, is itself able to induce effects on cyclin D1 and wound healing similar to those obtained with VD3. These results could be very useful in the future to better understand wound mechanisms and improve therapeutic interventions.
Highlights
The epidermis, derived from the ectoderm, is a keratinized stratified squamous epithelium that rests on the dermis, which houses skin appendages, many sensory neurons, and blood vessels
All strata are composed of different cell types: melanocytes, which derive from neural crest cells and produce melanin; Langerhans cells, which are of mesenchymal origin and are antigen-presenting cells; Merkel cells, which are modified epidermal cells that have sensory function for fine-touch; and keratinocytes, which represent the predominant cell type of epidermis
Keratinocytes originate in the basal stratum, where they are fed by dermis
Summary
The epidermis, derived from the ectoderm, is a keratinized stratified squamous epithelium that rests on the dermis, which houses skin appendages (sweat glands and hairs), many sensory neurons, and blood vessels. The epithelium includes different layers which, from inside to outside, are basale, spinosum, granulosum, lucidum, and corneum stratum. All strata are composed of different cell types: melanocytes, which derive from neural crest cells and produce melanin; Langerhans cells, which are of mesenchymal origin and are antigen-presenting cells; Merkel cells, which are modified epidermal cells that have sensory function for fine-touch; and keratinocytes, which represent the predominant cell type of epidermis. They move toward different strata up to the most superficial stratum, where the cells, which are practically composed of only keratin and are completely free of water, are lost. In actual fact, they contribute to somatosensation by releasing glutamate [2] and acetylcholine [3] or ATP [4] and can transduce nociceptive responses [5]
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