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Previous studies indicate that ion channels are mediators of bioelectricity promoting wound closure/regeneration in nonmammalian, lower vertebrate systems. The role of ion channels however in regeneration of wounds in mammalian systems that do not regenerate as adults is not yet defined. Using a mammalian model system that allows us to determine differentially expressed genes when skin regenerates and when skin does not regenerate after wound induction, we identified two potassium channels, kcnh2 and kcnj8, to be (1) differentially expressed between the two states and (2) highly expressed after wound induction at the nonregenerative state. We also found that kcnh2 small molecule inhibitor enhanced wound healing while kcnj8 small molecule inhibitor did not. In contrast, kcnj8 activator accelerated wound healing and even augmented the effect of kcnh2 inhibition. These results provide evidence for the first time that potassium channels may mediate skin wound healing and regeneration interactively., (© 2015 by the Wound Healing Society.)

Melanin protects the skin against DNA damage induced by direct absorption of sunlight's UV radiation. Yet, irradiating melanin in vitro or in cultured cells also generates active oxygen species such as superoxide, which can indirectly induce oxidative base lesions and DNA strand breaks. This photosensitization is greater for pheomelanin (yellow and red melanin) than for eumelanin (brown and black). The in vivo photosensitizing ability of melanin is unknown. We used congenic mice of black, yellow, and albino coat colors to investigate the induction of DNA lesions and apoptosis after exposure to predominantly UVB (280-320 nm) or UVA (320-400 nm) radiation. Cyclobutane pyrimidine dimers induced by direct UVB absorption were equal in all three strains, as was apoptosis measured as sunburn cells or as keratinocytes containing active caspase-3. However, terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL)-positive cells were approximately 3-fold more frequent in black and yellow mice after UVB or UVA irradiation than in albino. In epidermal sheets, TUNEL-positive cells lined the upper portion of the hair follicle, consistent with UV-induced photosensitization by melanin in the hair shaft. Because the concentration of eumelanin in black mice was three times that of pheomelanin in yellow mice, pheomelanin had 3-fold greater specific activity. We conclude that UV-irradiated melanin, particularly pheomelanin, photosensitizes adjacent cells to caspase-3 independent apoptosis, and this occurs at a frequency greater than the apoptosis induced by direct DNA absorption of UV. Melanin-induced apoptosis may contribute to the increased sensitivity of individuals with blonde and red hair to sunburn and skin cancer.

Cooperating with other signaling pathways, Wnt signaling controls cell proliferation, morphology, motility, and embryonic development destination and maintains the homeostasis of tissues including skin, blood, intestine, and brain by regulating somatic stem cells and their niches throughout adult life. Abnormal regulation of Wnt pathways leads to neoplastic proliferation in these tissues. Recent research shows that Wnt signaling is also associated with the regulation of cancer stem cells (CSCs) through a similar mechanism to that observed in normal adult stem cells. Thus, the Wnt/β-catenin signaling pathway has been intensively studied and characterized. For this review, we will focus on the regulation of the Wnt/β-catenin signaling pathway in skin cancer. With the important role in stemness and skin CSC proliferation, the Wnt/β-catenin signaling pathway and its elements have the potential to be targets for skin cancer therapy. [ABSTRACT FROM AUTHOR]