ABSTRACT
The dermis is mainly constructed by type I collagen fibers, which provide mechanical strength to the skin by building a frame-like structure, and by elastic fibers, which provide elasticity to respond to movements of the skin. The depletion of collagen fibers and the disappearance of oxytalan fibers, which are a type of elastic fiber, are characteristic changes in photoaged skin. Prostaglandin E2 (PGE2) is one of the chemical mediators involved in inflammation and is responsible for sunburn. Furthermore, it has been reported that PGE2 attenuates the production of collagen and the expression of elastic fiber-related factors in fibroblasts. Tranexamic acid (TXA), which is an anti-inflammatory medicine that inhibits plasmin, reduces the level of PGE2 secreted following UV exposure or after inflammatory stimulation. However, few reports have verified TXA as an anti-skin aging agent. In this study, we examined the potential of TXA as an anti-skin aging agent using repetitively UVA-irradiated fibroblasts as a model for fibroblasts located in chronically sun-exposed dermis. Repetitively UVA-irradiated fibroblasts had higher secretion levels of PGE2. In addition, fibroblasts repetitively irradiated with UVA or treated with PGE2 produced disrupted collagen and fibrillin-1 fibers. Treatment with TXA improved the formation of both types of fibers by repetitively UVA-irradiated fibroblasts by restoring the expression of fiber-related proteins at the mRNA and protein levels. Thus, these results demonstrate that TXA has potential as an anti-photoaging agent.
Subject(s)
Fibroblasts/drug effects , Skin Aging/drug effects , Skin/drug effects , Tranexamic Acid/pharmacology , Cell Line , Collagen/metabolism , Dinoprostone/metabolism , Drug Evaluation, Preclinical , Fibrillin-1/metabolism , Fibroblasts/metabolism , Fibroblasts/radiation effects , Humans , Skin/cytology , Skin/metabolism , Skin/radiation effects , Skin Aging/radiation effects , Ultraviolet Rays/adverse effectsABSTRACT
BACKGROUND: The induction of skin pigmentation by ultraviolet (UV) radiation has been shown to result from factors secreted from UV-exposed keratinocytes that enhance melanogenesis in melanosomes (MSs) and stimulates their transfer to keratinocytes. Among those factors, it has been reported that α-melanocyte stimulating hormone, which is converted from the precursor proopiomelanocortin (POMC) following UV exposure, stimulates the transfer of MSs from melanocytes to surrounding keratinocytes. OBJECTIVE: The purpose of this study was to evaluate the effects of a red pumpkin seed (RPS) extract on the transfer of MSs to keratinocytes and to clarify the involvement of reactive oxygen species (ROS) on the UVB-induced transfer of MSs. METHODS: The transfer of MSs into keratinocytes was examined by measuring the incorporation of fluorescent beads, which were used as pseudo-MSs. mRNA expression levels of POMC, Nrf2, and Nrf2-related genes were determined using real-time PCR. Intracellular ROS levels were estimated with H2 DCFDA. RESULTS: The incorporation of fluorescent beads into keratinocytes was enhanced by treatment with the conditioned medium (CM) from keratinocytes exposed to UVB or H2 O2 . UVB or H2 O2 exposed keratinocytes had an up-regulated mRNA expression level of POMC. Treatment of keratinocytes with the RPS extract enhanced their intracellular antioxidant system via the activation of Nrf2 signaling and suppressed their incorporation of fluorescent beads that had been stimulated by the CM from UVB or H2 O2 exposed keratinocytes. CONCLUSION: These results indicate that the RPS extract suppresses MS transfer stimulated by ROS generated following UVB exposure through the activation of Nrf2 signaling.