A Role for Neutral Sphingomyelinase in Wound Healing Induced by Keratinocyte Proliferation upon 1 α , 25-Dihydroxyvitamin D 3 Treatment

• Published in: International journal of molecular sciences 2019-08, Vol.20 (15)
• Main Authors: Patria, Federica Filomena, Ceccarini, Maria Rachele, Codini, Michela, Conte, Carmela, Perioli, Luana, Beccari, Tommaso, Albi, Elisabetta
• Format: Article
• Language: English
• Subjects: Calcitriol - pharmacology; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Humans; Keratinocytes - drug effects; Keratinocytes - metabolism; Sphingomyelin Phosphodiesterase - metabolism; Wound Healing - drug effects; Wound Healing - physiology
• ISSN: 1422-0067
• DOI: 10.3390/ijms20153634

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 1 , 25-dihydroxyvitamin D (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.