Violet Light Down-Regulates the Expression of Specific Differentiation Markers through Rhodopsin in Normal Human Epidermal Keratinocytes

Abstract

Several recent reports have demonstrated that photoreceptors are expressed in human skin. The rod and cone photoreceptor-like proteins are expressed in human skin and rhodopsin, long wavelength-opsin, and short wavelength-opsin are also present in cultured murine melanocytes. Furthermore, the photopigment rhodopsin is expressed in human melanocytes and is involved in ultraviolet A phototransduction which induces early melanin synthesis. In this study, we investigated whether rhodopsin is expressed and plays any physiological roles in the normal human epidermal keratinocytes (NHEKs). We found that rhodopsin was expressed and localized on the plasma membrane in NHEKs, and only violet light among several wavelengths within the visible range significantly increased the expression of rhodopsin mRNA. We further found that rhodopsin over-expression decreased the mRNA expression levels of keratinocyte differentiation markers, such as keratin-1 and keratin-10, and violet light also decreased the mRNA expression levels of keratinocyte differentiation markers and these decreased expression levels were recovered by a rhodopsin-directed siRNA. Moreover, we further demonstrated that violet light significantly decreased the phosphorylation levels of cAMP responsive element-binding protein (CREB) and that it more effectively decreased the phosphorylation of CREB when rhodopsin was over-expressed. In addition, we observed that pertussis toxin, a Gαi protein inhibitor, restored the rhodopsin-induced decrease in the differentiation markers in NHEKs. Taken together, these results suggest that rhodopsin down-regulates the expression levels of specific keratinocyte differentiation markers via the Gαi signaling pathway in NHEKs.

Expression of peropsin in human skin is related to phototransduction of violet light in keratinocytes

“…Rhodopsin, which was also found to be localized in the upper epidermal layer of human skin and OTC sections, [9] has been shown to modulate keratinocyte differentiation after exposure to 410 nm violet light. [3] It was believed that photoreceptors activated by shorter wavelength radiation (around 380-400 nm) were more likely to be localized in the upper epidermal layers nearer to the skin surface, because shorter wavelength radiation cannot penetrate into the skin as deep as longer wavelength radiation. [9] To summarize, our study is the first to identify peropsin in human skin and keratinocytes and demonstrate its contribution to phototransduction of short-wavelength, violet light, suggesting that the skin harbours photoreceptors that can indeed sense and distinguish various light …”

“…While many opsin members were originally discovered in the eye, several visual and non-visual opsins, including rhodopsin, short-wavelength opsin, melanopsin and neuropsin are also expressed in non-visual tissues such as the skin. [2,3] Previous study has suggested rhodopsin to contribute to UVA phototransduction in human epidermal melanocytes. [4] However, the role of these opsins in keratinocytes, the outermost skin layer constantly exposed to light, remains unclear.…”

Unconventional Roles of Opsins

“…Unexpectedly, the UVA response might occur via a G q -PLC signaling pathway (Bellono et al 2014, Wicks et al 2011). In keratinocytes, violet light downregulates expression of differentiation markers, and this effect is blunted upon siRNA-mediated suppression of rhodopsin (Kim et al 2013). An inhibitor of G i signaling prevents the light-induced downregulation of differentiation markers (Kim et al 2013), raising the possibility that rhodopsin couples to G t , G q , and G i cascades in rods, melanocytes, and keratinocytes, respectively.…”

“…In mammals, the long-held view was that photoreception is limited to the eye since enucleation of laboratory animals eliminates light entrainment (Nelson & Zucker 1981). However, there is evidence that mammals can detect light in skin (Haltaufderhyde et al 2015, Kim et al 2013, Toh et al 2016, Tsutsumi et al 2009, Wicks et al 2011), the brain (Sun et al 2016, Wade et al 1988), and in blood vessels (Sikka et al 2014). Non-mammalian vertebrates, such as fish and birds, have extra-ocular light sensory cells in multiple tissues, including the pineal (Bailey & Cassone 2004, Chaurasia et al 2005, Okano et al 1994), the hypothalamus (Fischer et al 2013, Halford et al 2009), and in dermal melanophores (Provencio et al 1998b).…”

The Biological Mechanisms and Behavioral Functions of Opsin-Based Light Detection by the Skin

“…It is likely that many of these pigments are involved in multiple non-visual tasks (e.g., modulation of peripheral clocks, photoisomerization, UV detection, and DNA repair); nonetheless, it would not be unexpected if many of these light-activated proteins also played a photosensory role in localized pigment dispersion, a hypothesis that warrants further investigation. Of particular interest is the observation that ∼40% of non-mammalian opsin gene classes are conserved in the mammalian lineage (Davies et al, 2015), some of which (e.g., OPN1SW; rhodopsin-1, RH1; panopsin, OPN3, and neuropsin, OPN5) are expressed in dermal tissue of mice (Kojima et al, 2011;de Assis et al, 2016) and humans (Tsutsumi et al, 2009;Kim et al, 2013;Haltaufderhyde et al, 2015). Their functional roles are currently unknown; however, it has been suggested that they might be involved in the detection of solar radiation and may induce photo-protective cellular and behavioral mechanisms.…”