Abstract:The human skin has previously been described to be affected by light; however, the underlying mechanism remains unknown. OPN4 (melanopsin) expression was first identified in the skin of amphibians; however, whether it is also expressed and functioned in the human skin has not yet been identified. Here, we show that OPN4 was expressed in the human skin tissue and cultures of isolated keratinocytes, melanocytes and fibroblasts. Additionally, Ca2+ influx in vitro and ex vivo and phosphorylation of extracellular s… Show more
“…In particular, the skin is an interesting peripheral organ in which opsin expression was first reported almost 20 years ago [23]. Since then, an increasing number of studies have demonstrated the presence and functionality of opsins in the skin [24][25][26][27][28][29][30][31][33][34][35][36][40][41][42]52,58]. Recently, the role of opsins in the skin and other peripheral tissues has been reviewed [59,60].…”
Section: Discussionmentioning
confidence: 99%
“…Functional studies were only performed almost a decade later by Oancea's lab pioneering reports [25][26][27]. To the present day, the photosensitive system of the skin has been shown to participate in murine and human: pigmentary responses [25][26][27][28][29][30][31], differentiation processes of keratinocytes [32,33], hair follicle growth [34], UVA-induced photoaging [35], cellular growth and apoptosis in response to UVA radiation [28], and UV-and blue light-induced calcium influx [25,27,36].…”
Skin melanocytes harbor a complex photosensitive system comprised of opsins, which were shown, in recent years, to display light- and thermo-independent functions. Based on this premise, we investigated whether melanopsin, OPN4, displays such a role in normal melanocytes. In this study, we found that murine Opn4KO melanocytes displayed a faster proliferation rate compared to Opn4WT melanocytes. Cell cycle population analysis demonstrated that OPN4KO melanocytes exhibited a faster cell cycle progression with reduced G0–G1, and highly increased S and slightly increased G2/M cell populations compared to the Opn4WT counterparts. Expression of specific cell cycle-related genes in Opn4KO melanocytes exhibited alterations that corroborate a faster cell cycle progression. We also found significant modification in gene and protein expression levels of important regulators of melanocyte physiology. PER1 protein level was higher while BMAL1 and REV-ERBα decreased in Opn4KO melanocytes compared to Opn4WT cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in Opn4KO melanocytes, which is in line with a higher proliferative capability. Taken altogether, we demonstrated that OPN4 regulates cell proliferation, cell cycle, and affects the expression of several important factors of the melanocyte physiology; thus, arguing for a putative tumor suppression role in melanocytes.
“…In particular, the skin is an interesting peripheral organ in which opsin expression was first reported almost 20 years ago [23]. Since then, an increasing number of studies have demonstrated the presence and functionality of opsins in the skin [24][25][26][27][28][29][30][31][33][34][35][36][40][41][42]52,58]. Recently, the role of opsins in the skin and other peripheral tissues has been reviewed [59,60].…”
Section: Discussionmentioning
confidence: 99%
“…Functional studies were only performed almost a decade later by Oancea's lab pioneering reports [25][26][27]. To the present day, the photosensitive system of the skin has been shown to participate in murine and human: pigmentary responses [25][26][27][28][29][30][31], differentiation processes of keratinocytes [32,33], hair follicle growth [34], UVA-induced photoaging [35], cellular growth and apoptosis in response to UVA radiation [28], and UV-and blue light-induced calcium influx [25,27,36].…”
Skin melanocytes harbor a complex photosensitive system comprised of opsins, which were shown, in recent years, to display light- and thermo-independent functions. Based on this premise, we investigated whether melanopsin, OPN4, displays such a role in normal melanocytes. In this study, we found that murine Opn4KO melanocytes displayed a faster proliferation rate compared to Opn4WT melanocytes. Cell cycle population analysis demonstrated that OPN4KO melanocytes exhibited a faster cell cycle progression with reduced G0–G1, and highly increased S and slightly increased G2/M cell populations compared to the Opn4WT counterparts. Expression of specific cell cycle-related genes in Opn4KO melanocytes exhibited alterations that corroborate a faster cell cycle progression. We also found significant modification in gene and protein expression levels of important regulators of melanocyte physiology. PER1 protein level was higher while BMAL1 and REV-ERBα decreased in Opn4KO melanocytes compared to Opn4WT cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in Opn4KO melanocytes, which is in line with a higher proliferative capability. Taken altogether, we demonstrated that OPN4 regulates cell proliferation, cell cycle, and affects the expression of several important factors of the melanocyte physiology; thus, arguing for a putative tumor suppression role in melanocytes.
“… 12 Pulmonary arterial diameter has also recently been shown to be light sensitive and use an Opn4- dependent mechanism. 61 In human tissue, it has been demonstrated that skin expresses Opn1sw , Opn2 , Opn3, Opn4, and Opn5 , 65 – 67 suggesting that extraretinal, opsin-mediated photoreception may extend to humans as well.…”
Autonomous molecular circadian clocks are present in the majority of mammalian tissues. These clocks are synchronized to phases appropriate for their physiologic role by internal systemic cues, external environmental cues, or both. The circadian clocks of the in vivo mouse cornea synchronize to the phase of the brain's master clock primarily through systemic cues, but ex vivo corneal clocks entrain to environmental light cycles. We evaluated the underlying mechanisms of this difference. METHODS. Molecular circadian clocks of mouse corneas were evaluated in vivo and ex vivo for response to environmental light. The presence of opsins and effect of genetic deletion of opsins were evaluated for influence on circadian photoresponses. Opn5-expressing cells were identified using Opn5 Cre ;Ai14 mice and RT-PCR, and they were characterized using immunocytochemistry. RESULTS. Molecular circadian clocks of the cornea remain in phase with behavioral circadian locomotor rhythms in vivo but are photoentrainable in tissue culture. After fullthickness incision or epithelial debridement, expression of the opsin photopigment Opn5 is induced in the cornea in a subset of preexisting epithelial cells adjacent to the wound site. This induction coincides with conferral of direct, short-wavelength light sensitivity to the circadian clocks throughout the cornea. CONCLUSIONS. Corneal circadian rhythms become photosensitive after wounding. Opn5 gene function (but not Opn3 or Opn4 function) is necessary for induced photosensitivity. These results demonstrate that opsin-dependent direct light sensitivity can be facultatively induced in the murine cornea.
“…Although individuals are exposed to visible light during daytime, little is known regarding the effects of visible light on our skin, except for the eye. Interestingly, photoreceptors that respond to various wavelengths of sunlight have been identified in the skin and their signaling mechanisms have been elucidated (Wicks et al 2011 ; Kim et al 2013 ; de Assis et al 2018 ; Regazzetti et al 2018 ; Kusumoto et al 2020 ).…”
Section: Introductionmentioning
confidence: 99%
“…OPN4 is observed in human keratinocytes, melanocytes, and fibroblasts. Blue light stimulates Ca 2+ influx and the phosphorylation of extracellular signal-regulated kinases 1/2 in an intensity-dependent manner (Kusumoto et al 2020 ) ( Figure 1 ). Figure 1.…”
The skin protects our body from various external factors, such as chemical and physical stimuli, microorganisms, and sunlight. Sunlight is a representative environmental factor that considerably influences the physiological activity of our bodies. The molecular mechanisms and detrimental effects of ultraviolet rays (UVR) on skin have been thoroughly investigated. Chronic exposure to UVR generally causes skin damage and eventually induces wrinkle formation and reduced elasticity of the skin. Several studies have shown that infrared rays (IR) also lead to the breakdown of collagen fibers in the skin. However, several reports have demonstrated that the appropriate use of UVR or IR can have beneficial effects on skin-related diseases. Additionally, it has been revealed that visible light of different wavelengths has various biological effects on the skin. Interestingly, several recent studies have reported that photoreceptors are also expressed in the skin, similar to those in the eyes. Based on these data, I discuss the various physiological effects of sunlight on the skin and provide insights on the use of phototherapy, which uses a specific wavelength of sunlight as a non-invasive method, to improve skin-related disorders.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
