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Circadian Oscillations in Skin
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This entry is adapted from the peer-reviewed paper 10.3390/ijms24065635

The term circadian rhythm, defined by Franz Halberg, a pioneer of chronobiology, in 1959, was originally adapted from Greek. It is a hybrid of the words “circa” and “day”, meaning approximately 24 h or a day. In his later work, Halberg described biological cycles, which are an overlay of oscillations that occur in mammals. Circadian rhythm is closely linked to immunological processes and skin homeostasis, and its desynchrony can be linked to the perturbation of the skin. The interplay between circadian rhythm and annual, seasonal oscillations, as well as the impact of these periodic events on the skin, is described.

circadian rhythms entrainment skin

1. Influence of the Circadian Clock on Immune Response of the Skin

The components of the circadian clock machinery are crucial to the development and functioning of a robust immune system. Indeed, most immune cell lineages have intrinsic clocks that govern their maturation, migration, differentiation, and function. An example is NFIL3, which is responsible for the development and maintenance of a population of interferon-gamma (IFN-γ) producing group 1 innate lymphoid cells and NK cells [1]. This, in turn, can be linked to the rhythmic activation of IFN-sensitive gene pathways in the skin, including a key transcription factor IFN regulatory factor 7 (Irf7) via Toll-like receptor 7 (TLR7). The induction of TLR7 is used in in vivo models to study psoriasiform inflammation [2][3]. Similarly, ROR-α expression is thought to be increased in activated phenotype Treg cells in mouse skin [4]. Activated Treg cells expressing ROR-α have been shown to attenuate the function of group 2 innate lymphoid cells that reside in the skin. This has been shown to limit allergic skin inflammation in models of atopic dermatitis mediated by type II cytokines including IL-4, IL-5, and IL-13, (Figure 1). Left unchecked, these interleukins would possibly involve the recruitment of TH2 cells into the skin, leading to increased CCL17 and CCL22 production [4][5][6]. Furthermore, the circadian clock determines the rhythm with which immune cells circulate or migrate into tissues. The adhesion molecules ICAM-1 and VCAM-1 on endothelial cells vary based on the degree of inflammation, as well as rhythmicity, and act as homing signals for leukocytes in homeostasis, as well as inflammation [7]. Moreover, in skin, CD44 appears to be the adhesion molecule that varies in a circadian manner and acts as a honing signal for leucocytes in endothelial cells that constitute the capillaries of the dermis [7][8]. This circadian rhythmic variation prevents overactivation of the immune system when an external challenge is unlikely, and preparation of the immune system in more active phases of the day when a host is more likely to be faced with a challenge of a pathogen [7]. This can also be seen in the enhanced expression of the antimicrobial peptide retinoic acid receptor responder 2 (Rarres2), cathelicidin antimicrobial peptide (Camp), and beta defensin 1 (Defb1) in phases of heightened activity [7][9]. Thus, although the immune system remains constantly vigilant and primed to mount a response to antigens, research into the influence of circadian rhythm on the immune system suggests an existence of a partition of the day into two phases. The first phase is one of heightened vigilance during waking hours where most activity occurs and an immune onslaught is most likely. This is followed by a recovery phase where resolution of inflammation and tissue repair occurs in the entire organism including the skin (Figure 1) [10].
The modulation of the two immunological pathways in skin has been shown to be influenced by glucocorticoids and nutrient intake, which act as zeitgebers. Of these, glucocorticoids have been studied in greater depth and have been linked to the central clock in the SCN [11][12][13][14]. The secretion of adrenocorticotropin (ATCH) from the anterior pituitary gland is under the control of the SCN [10]. This endocrine hormone, in turn, regulates the release of glucocorticoid hormones from the adrenal glands, which then give tact to the circadian clocks in peripheral tissues, as well as demonstrating immune regulatory function. However, ablation of the adrenal glands does not lead to loss of circadian oscillation in the skin and other peripheral tissue. In addition to the fact that skin can be directly entrained, this retention of circadian rhythm could be explained by the fact that keratinocytes of the epidermal layer in the skin are capable of regulating immune function by de novo synthesis of glucocorticoids via 11ß-hydroxylase (Cyp11b1), in addition to reactivation of inactive glucocorticoids via the enzyme 11ß-hydroxysteroid dehydrogenase type 1 (HSD11B1) [11][15].
Figure 1. Influence of the circadian clock on skin immune response and homeostasis. The influence of the circadian clock on the immune responses in the skin allows for the day to be partitioned into a recovery phase and a heightened vigilance phase. Circadian oscillations of cytokines, adhesion molecules, and antimicrobial peptides have been observed. In the maintenance of epidermal homeostasis, the day can be divided into five succussive 4–5 h phases where distinct cellular processes occur. Further details can be found in [16]. Since the information here is a cumulation of information from studies performed in mice (nocturnal) models and cells, as well as human (diurnal) tissue and cells, the sinusoid in this figure serves a representational purpose only.
Thus far, the close interlinking of the immune responses and circadian rhythm has been established, and hence it can be correctly assumed that inflammation can disrupt the local, peripheral circadian clocks, as well as the central clock in the SCN. Recent reports implicate the NF-kB pathway in playing a central role in causing these perturbations [17][18][19]. In addition to this pathway, researchers have shown that TNF-α, IFN-γ, IL-1, and LPS are capable of disrupting the oscillations of a core clock gene and the genes that they control (Figure 1) [10][13][20][21][22][23][24][25][26]. In particular, TNF-α has been identified as a mediator of circadian phase changes. It alters the expression of a number of core components of the circadian clock machinery and has been attributed to the ability to inhibit the binding of BMAL1:CLOCK to its E-box promoter. Furthermore, disruption of the circadian clock can cause disruptions to the immune system. In a chronic jet lag mouse model, even a single exposure to jet lag was able to worsen the response to a high dose LPS challenge [25]. More specifically for skin, when tested in a mouse model for human allergic contact dermatitis, the T-cell mediated chronic hypersensitivity response was triggered by the disruption of the circadian clock. This pathology manifests together with heightened IgE level and increased mast cell numbers [27][28]. In another mouse model where psoriasis was induced via TLR7, CLOCK and Per2 were found to regulate the severity of psoriasis via the direct modulation of the expression of IL23R (Figure 1) [3]. In humans, epidemiological studies have also associated shift work, where the circadian clock is assumed to be disrupted, with higher risk of psoriasis [27][29]. These inflammatory reactions brought on by circadian disruptions are also likely to compromise the integrity of the skin, since, in human keratinocytes, TIMP3, which is a broad spectrum inhibitor of extracellular matrix (ECM)-degrading enzymes (MMPs, ADAM, ADAMTS), is likely to be under CLOCK control [2][12][13][30][31][32][33][34]. Thus, the magnitude of immune responses in the skin are profoundly impacted by the circadian system. In turn, disruption of the circadian rhythm of the skin leads to immune hyperactivity or an aberrant immune response that can manifest as pathologies such as dermatitis or psoriasis. A better understanding of the circadian rhythm and the immune system could help in the development of therapeutic approaches to treat diseased skin, especially since skin permeability also varies in a circadian manner [35]. Circadian transcriptome analysis has already delved into the oscillatory expression pattern of rhythmic genes in tissues (including skin) from a human, a non-human primate (baboon), and a mouse [36][37][38][39]. The core clock components and their immediate output targets were the most enriched transcripts across tissues. These studies also found that epidermal molecular oscillations are more robust than those of the dermal fibroblasts [40]. Non-sun-exposed skin showed the strongest nocturnal preference, whereas sun-exposed skin showed diurnal preference [37]. Furthermore, a majority of therapeutic targets are influenced by circadian oscillations, and many of the drugs that target these genes have a short half-life (<6 h), such that the circadian cycling of their targets could be consequential in the efficacy of administered treatment [36][37]. In an effort to take these oscillations into account, efforts have been made to monitor the circadian rhythm of a patient via biomarkers in the skin [40][41]. Although this approach has the potential to make big advancements in the field of circadian medicine, starting with the temporal adjustment of doses, the interference of circadian phases from peripheral tissue should be done cautiously.

2. Influence of the Circadian Clock on Skin Homeostasis and Stress Mediation

As in the case of the immune cells, circadian oscillations are observed in keratinocytes and melanocytes of the epidermis and the fibroblasts of the dermis [42][43]. The circadian clock machinery responsible for oscillations impact the metabolic processes of these cells and has an impact of tissue homeostasis. The epidermis is generated from epidermal stem cells in the basal layer that undergo asymmetric cell division, giving rise to either daughter stem cells or keratinocytes that will undergo a process of differentiation and desquamation to form the horny layer of the stratum corneum. It takes cells approximately 14 days for epidermal stem cells to end up as part of the stratum corneum. During this 2-week period, the process of differentiation does not occur continuously, but instead appears to occur in five sequential 24-h cyclic phases coordinated by the circadian clock. When studied via gene expression, each phase lasts for 4–5 h (Figure 1) [16][30][44]. For undifferentiated keratinocytes, the first phase includes cells being primed for differentiation with the upregulation of genes including klf9 and notch3 [16][45]. In the second and third phases, calcium dependent differentiation is triggered, together with the metabolic process associated with it. These three phases correspond to the late night to early morning hours, and vitamin D metabolism is also upregulated here. In the next two phases, genes associated with DNA damage protection and stress mediation are upregulated in undifferentiated keratinocytes, along with genes involved in preparing the onset of the next cycle of cell division and differentiation. In differentiated keratinocytes, the genes upregulated in the first three phases under circadian control remained similar to their undifferentiated counterparts, but included genes associated with DNA damage protection and repair, indicating constant vigilance against assault to the genetic code (Figure 1). In the next two phases, differentiated keratinocytes seem to shift their focus to building a defensive barrier with genes for differentiation and keratin organization being upregulated. This is likely to include the surface lipids of the skin that are under clock control and contribute to the skin barrier [16][46]. The differentiation process is not only dependent on the expression of the clock genes, but also their amplitude. The differentiation of the keratinocytes increases the amplitude of oscillation of PER1-2 and DBP, whereas that of BMAL1 is decreased. Disturbances to this oscillation, by overexpressing PER1 and PER2, or by decreasing the expression of CRY1 and CRY2, leads to spontaneous oscillations, which would perturb the division of the epidermal stem cells, and consequently also the homeostasis of the epidermis [15]. Autophagy is also closely linked to maintaining skin homeostasis. In the liver, the rhythmicity of autophagy is coordinated via C/EBPß, and in skin fibroblasts, the desynchrony of autophagy with age was reported by monitoring the gene expression of the marker LC3B and PER2 [31][47][48]. Although the interplay of autophagy, the circadian clock, and aging continue to be of interest, the role of these processes in skin cells has yet to be clarified [49].
Melanocytes and dermal fibroblasts have also shown to possess functioning circadian clock machinery, but the amplitude of oscillations appear smaller than that of keratinocytes. Despite this, the circadian clock plays a functional role in melanocytes by controlling the abundance of melanosomes, as well as the expression of melanin synthesis enzyme, Tyrosinase and the phosphorylation of MITF, which increases when BMAL1 or PER1 are silenced [50][51]. The protein OPN4 has been shown to affect the molecular clock components and their responsiveness to classical clock activators in melanocytes. Knocking out OPN4 in melanocytes resulted in rapid cell cycle progression and increased cellular proliferation, which correlated with the altered gene expression of MITF and the core circadian clock components [52]. The impact of the function of the circadian clock on dermal fibroblasts is yet to be characterized. However, the influence of circadian rhythm on the synthesis and secretion of Type I collagen, a major component of the ECM of the dermis, is already known [53][54]. Furthermore, the efficiency of migration and adhesion of fibroblasts modulated via actin dynamics was found to be circadian regulated [55]. This has been underlined by the correlation found from a database analysis indicating daytime wounds heal approximately 60% faster than wounds occurring at night. The nuclear protein NONO has been suggested as a possible molecular link between wound healing and the circadian rhythm of fibroblasts [56].
Thus, not only is normal function of skin impacted by circadian oscillations, but also the ability of skin to deal with stress is influenced by the cellular clock. As described above, the genes involved in DNA damage protection and repair in the epidermis are under clock control, as well as genes that mediate oxidative stress responses, in particular NRF2, the peroxiredoxins, glutathione peroxidase, and sestrins [57][58][59][60][61][62]. It can be hypothesized that these genes are under the control of the circadian clock so that the skin may prepare for stress mediation only when the onset of this stress is likely, i.e., during active hours with maintenance undertaken during non-active hours. This is corroborated with the fact that, in human skin, the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1) was higher at night [63]. This is particularly important in the case of melanocytes, since they can accumulate DNA damage long after UV exposure, via melanin excitation [64][65]. In mouse skin, the xeroderma pigmentosum group A (XPA) protein, which is the rate limiting subunit of excision repair, exhibited circadian rhythmicity; thus, when mouse skin was exposed to UV irradiation, the likelihood of development of skin cancer after UV was linked to the time of day [66][67].
The evolutionary conserved hormone melatonin is also responsible for combating DNA damage and oxidative stress, as well as maintaining skin homeostasis [68]. This corelates with the finding that the circadian rhythm of melanin secretion is disrupted in psoriatic patients [69]. Since this molecule and its related metabolites are free radicle scavenges, it is capable of stress mediation [58][68]. Skin pigmentation and hair growth are also controlled by melatonin; its activity may also be influenced by the skin’s circadian clock [50][51][70]. Melatonin has also been implicated in the control of skin and body temperature in a circadian manner. In rat skin, the circadian clock machinery dermal fibroblasts is capable of using melatonin as an internal signal to fine-tune its oscillations, with temperature being used as an external queue [71]. Although melatonin is secreted from the pineal gland and synthesis is regulated by the degradation of arylalkylamine N-acetyltransferase (AANAT) in its synthetic pathway via light detected in the retina, the concentration of melanin in the skin can be far greater than that present in serum [72][73][74]. Therefore, further research is needed to disentangle the role of locally synthesized melatonin in the skin and its circadian clock.

References

  1. Greenberg, E.N.; Marshall, M.E.; Jin, S.; Venkatesh, S.; Dragan, M.; Tsoi, L.C.; Gudjonsson, J.E.; Nie, Q.; Takahashi, J.S.; Andersen, B. Circadian control of interferon-sensitive gene expression in murine skin. Proc. Natl. Acad. Sci. USA 2020, 117, 5761–5771.
  2. Scheiermann, C.; Gibbs, J.; Ince, L.; Loudon, A. Clocking in to immunity. Nat. Rev. Immunol. 2018, 18, 423–437.
  3. Ando, N.; Nakamura, Y.; Aoki, R.; Ishimaru, K.; Ogawa, H.; Okumura, K.; Shibata, S.; Shimada, S.; Nakao, A. Circadian Gene Clock Regulates Psoriasis-Like Skin Inflammation in Mice. J. Investig. Dermatol. 2015, 135, 3001–3008.
  4. Malhotra, N.; Leyva-Castillo, J.M.; Jadhav, U.; Barreiro, O.; Kam, C.; O’Neill, N.K.; Meylan, F.; Chambon, P.; von Andrian, U.H.; Siegel, R.M.; et al. RORalpha-expressing T regulatory cells restrain allergic skin inflammation. Sci. Immunol. 2018, 3, eaao6923.
  5. Chiricozzi, A.; Maurelli, M.; Peris, K.; Girolomoni, G. Targeting IL-4 for the Treatment of Atopic Dermatitis. Immunotargets Ther. 2020, 9, 151–156.
  6. Purwar, R.; Werfel, T.; Wittmann, M. IL-13-stimulated human keratinocytes preferentially attract CD4+CCR4+ T cells: Possible role in atopic dermatitis. J. Investig. Dermatol. 2006, 126, 1043–1051.
  7. He, W.; Holtkamp, S.; Hergenhan, S.M.; Kraus, K.; de Juan, A.; Weber, J.; Bradfield, P.; Grenier, J.M.P.; Pelletier, J.; Druzd, D.; et al. Circadian Expression of Migratory Factors Establishes Lineage-Specific Signatures that Guide the Homing of Leukocyte Subsets to Tissues. Immunity 2018, 49, 1175–1190.e7.
  8. Zoller, M.; Gupta, P.; Marhaba, R.; Vitacolonna, M.; Freyschmidt-Paul, P. Anti-CD44-mediated blockade of leukocyte migration in skin-associated immune diseases. J. Leukoc. Biol. 2007, 82, 57–71.
  9. Bilska, B.; Zegar, A.; Slominski, A.T.; Kleszczynski, K.; Cichy, J.; Pyza, E. Expression of antimicrobial peptide genes oscillates along day/night rhythm protecting mice skin from bacteria. Exp. Dermatol. 2021, 30, 1418–1427.
  10. Curtis, A.M.; Bellet, M.M.; Sassone-Corsi, P.; O’Neill, L.A. Circadian clock proteins and immunity. Immunity 2014, 40, 178–186.
  11. San Phan, T.; Schink, L.; Mann, J.; Merk, V.M.; Zwicky, P.; Mundt, S.; Simon, D.; Kulms, D.; Abraham, S.; Legler, D.F. Keratinocytes control skin immune homeostasis through de novo–synthesized glucocorticoids. J. Sci. Adv. 2021, 7, eabe0337.
  12. Palomino-Segura, M.; Hidalgo, A. Circadian immune circuits. J. Exp. Med. 2021, 218, e20200798.
  13. Waggoner, S.N. Circadian Rhythms in Immunity. Curr. Allergy Asthma Rep. 2020, 20, 2.
  14. Oster, H.; Challet, E.; Ott, V.; Arvat, E.; de Kloet, E.R.; Dijk, D.-J.; Lightman, S.; Vgontzas, A.; van Cauter, E. The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids. Endocr. Rev. 2016, 38, 3–45.
  15. Buhr, E.D.; Vemaraju, S.; Diaz, N.; Lang, R.A.; van Gelder, R.N. Neuropsin (OPN5) Mediates Local Light-Dependent Induction of Circadian Clock Genes and Circadian Photoentrainment in Exposed Murine Skin. Curr. Biol. 2019, 29, 3478–3487.e4.
  16. Janich, P.; Toufighi, K.; Solanas, G.; Luis, N.M.; Minkwitz, S.; Serrano, L.; Lehner, B.; Benitah, S.A. Human epidermal stem cell function is regulated by circadian oscillations. Cell Stem Cell 2013, 13, 745–753.
  17. Shen, Y.; Endale, M.; Wang, W.; Morris, A.R.; Francey, L.J.; Harold, R.L.; Hammers, D.W.; Huo, Z.; Partch, C.L.; Hogenesch, J.B.; et al. NF-kappaB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1. PLoS Genet. 2021, 17, e1009933.
  18. Hong, H.K.; Maury, E.; Ramsey, K.M.; Perelis, M.; Marcheva, B.; Omura, C.; Kobayashi, Y.; Guttridge, D.C.; Barish, G.D.; Bass, J. Requirement for NF-kappaB in maintenance of molecular and behavioral circadian rhythms in mice. Genes Dev. 2018, 32, 1367–1379.
  19. Haspel, J.A.; Chettimada, S.; Shaik, R.S.; Chu, J.H.; Raby, B.A.; Cernadas, M.; Carey, V.; Process, V.; Hunninghake, G.M.; Ifedigbo, E.; et al. Circadian rhythm reprogramming during lung inflammation. Nat. Commun. 2014, 5, 4753.
  20. Abreu, M.; Basti, A.; Genov, N.; Mazzoccoli, G.; Relogio, A. The reciprocal interplay between TNFalpha and the circadian clock impacts on cell proliferation and migration in Hodgkin lymphoma cells. Sci. Rep. 2018, 8, 11474.
  21. Yoshida, K.; Hashiramoto, A.; Okano, T.; Yamane, T.; Shibanuma, N.; Shiozawa, S. TNF-alpha modulates expression of the circadian clock gene Per2 in rheumatoid synovial cells. Scand. J. Rheumatol. 2013, 42, 276–280.
  22. Bashir, M.M.; Sharma, M.R.; Werth, V.P. TNF-alpha production in the skin. Arch. Dermatol. Res. 2009, 301, 87–91.
  23. Cavadini, G.; Petrzilka, S.; Kohler, P.; Jud, C.; Tobler, I.; Birchler, T.; Fontana, A. TNF-alpha suppresses the expression of clock genes by interfering with E-box-mediated transcription. Proc. Natl. Acad. Sci. USA 2007, 104, 12843–12848.
  24. Cermakian, N.; Lange, T.; Golombek, D.; Sarkar, D.; Nakao, A.; Shibata, S.; Mazzoccoli, G. Crosstalk between the circadian clock circuitry and the immune system. Chronobiol. Int. 2013, 30, 870–888.
  25. Castanon-Cervantes, O.; Wu, M.; Ehlen, J.C.; Paul, K.; Gamble, K.L.; Johnson, R.L.; Besing, R.C.; Menaker, M.; Gewirtz, A.T.; Davidson, A.J. Dysregulation of inflammatory responses by chronic circadian disruption. J. Immunol. 2010, 185, 5796–5805.
  26. Okada, K.; Yano, M.; Doki, Y.; Azama, T.; Iwanaga, H.; Miki, H.; Nakayama, M.; Miyata, H.; Takiguchi, S.; Fujiwara, Y.; et al. Injection of LPS causes transient suppression of biological clock genes in rats. J. Surg. Res. 2008, 145, 5–12.
  27. Paganelli, R.; Petrarca, C.; di Gioacchino, M. Biological clocks: Their relevance to immune-allergic diseases. Clin. Mol. Allergy 2018, 16, 1.
  28. Takita, E.; Yokota, S.; Tahara, Y.; Hirao, A.; Aoki, N.; Nakamura, Y.; Nakao, A.; Shibata, S. Biological clock dysfunction exacerbates contact hypersensitivity in mice. Br. J. Dermatol. 2013, 168, 39–46.
  29. Wu, G.; Ruben, M.D.; Schmidt, R.E.; Francey, L.J.; Smith, D.F.; Anafi, R.C.; Hughey, J.J.; Tasseff, R.; Sherrill, J.D.; Oblong, J.E.; et al. Population-level rhythms in human skin with implications for circadian medicine. Proc. Natl. Acad. Sci. USA 2018, 115, 12313–12318.
  30. Sherratt, M.J.; Hopkinson, L.; Naven, M.; Hibbert, S.A.; Ozols, M.; Eckersley, A.; Newton, V.L.; Bell, M.; Meng, Q.J. Circadian rhythms in skin and other elastic tissues. Matrix Biol. 2019, 84, 97–110.
  31. Matsui, M.S.; Pelle, E.; Dong, K.; Pernodet, N. Biological Rhythms in the Skin. Int. J. Mol. Sci. 2016, 17, 801.
  32. Fan, D.; Kassiri, Z. Biology of Tissue Inhibitor of Metalloproteinase 3 (TIMP3), and Its Therapeutic Implications in Cardiovascular Pathology. Front. Physiol. 2020, 11, 661.
  33. Park, S.; Kim, K.; Bae, I.H.; Lee, S.H.; Jung, J.; Lee, T.R.; Cho, E.G. TIMP3 is a CLOCK-dependent diurnal gene that inhibits the expression of UVB-induced inflammatory cytokines in human keratinocytes. FASEB J. 2018, 32, 1510–1523.
  34. Yeom, M.; Lee, H.; Shin, S.; Park, D.; Jung, E. PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP. Molecules 2018, 23, 745.
  35. Yosipovitch, G.; Xiong, G.L.; Haus, E.; Sackett-Lundeen, L.; Ashkenazi, I.; Maibach, H.I. Time-dependent variations of the skin barrier function in humans: Transepidermal water loss, stratum corneum hydration, skin surface pH, and skin temperature. J. Investig. Dermatol. 1998, 110, 20–23.
  36. Ruben, M.D.; Wu, G.; Smith, D.F.; Schmidt, R.E.; Francey, L.J.; Lee, Y.Y.; Anafi, R.C.; Hogenesch, J.B. A database of tissue-specific rhythmically expressed human genes has potential applications in circadian medicine. Sci. Transl. Med. 2018, 10, eaat8806.
  37. Wucher, V.; Sodaei, R.; Amador, R.; Irimia, M.; Guigo, R. Day-night and seasonal variation of human gene expression across tissues. PLoS Biol. 2023, 21, e3001986.
  38. Zhang, R.; Lahens, N.F.; Ballance, H.I.; Hughes, M.E.; Hogenesch, J.B. A circadian gene expression atlas in mammals: Implications for biology and medicine. Proc. Natl. Acad. Sci. USA 2014, 111, 16219–16224.
  39. Mure, L.S.; Le, H.D.; Benegiamo, G.; Chang, M.W.; Rios, L.; Jillani, N.; Ngotho, M.; Kariuki, T.; Dkhissi-Benyahya, O.; Cooper, H.M.; et al. Diurnal transcriptome atlas of a primate across major neural and peripheral tissues. Science 2018, 359, eaao0318.
  40. Wu, G.; Ruben, M.D.; Francey, L.J.; Smith, D.F.; Sherrill, J.D.; Oblong, J.E.; Mills, K.J.; Hogenesch, J.B. A population-based gene expression signature of molecular clock phase from a single epidermal sample. Genome Med. 2020, 12, 73.
  41. Akashi, M.; Soma, H.; Yamamoto, T.; Tsugitomi, A.; Yamashita, S.; Yamamoto, T.; Nishida, E.; Yasuda, A.; Liao, J.K.; Node, K. Noninvasive method for assessing the human circadian clock using hair follicle cells. Proc. Natl. Acad. Sci. USA 2010, 107, 15643–15648.
  42. Sandu, C.; Liu, T.; Malan, A.; Challet, E.; Pevet, P.; Felder-Schmittbuhl, M.P. Circadian clocks in rat skin and dermal fibroblasts: Differential effects of aging, temperature and melatonin. Cell. Mol. Life Sci. 2015, 72, 2237–2248.
  43. Sandu, C.; Dumas, M.; Malan, A.; Sambakhe, D.; Marteau, C.; Nizard, C.; Schnebert, S.; Perrier, E.; Challet, E.; Pevet, P.; et al. Human skin keratinocytes, melanocytes, and fibroblasts contain distinct circadian clock machineries. Cell. Mol. Life Sci. 2012, 69, 3329–3339.
  44. Eckhart, L.; Lippens, S.; Tschachler, E.; Declercq, W. Cell death by cornification. Biochim. Biophys. Acta 2013, 1833, 3471–3480.
  45. Sporl, F.; Korge, S.; Jurchott, K.; Wunderskirchner, M.; Schellenberg, K.; Heins, S.; Specht, A.; Stoll, C.; Klemz, R.; Maier, B.; et al. Kruppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes. Proc. Natl. Acad. Sci. USA 2012, 109, 10903–10908.
  46. Jia, Y.; Zhou, M.; Huang, H.; Gan, Y.; Yang, M.; Ding, R. Characterization of circadian human facial surface lipid composition. Exp. Dermatol. 2019, 28, 858–862.
  47. Ma, D.; Panda, S.; Lin, J.D. Temporal orchestration of circadian autophagy rhythm by C/EBPbeta. EMBO J. 2011, 30, 4642–4651.
  48. Pernodet, N.; Dong, K.; Pelle, E. Autophagy in human skin fibroblasts: Comparison between young and aged cells and evaluation of its cellular rhythm and response to Ultraviolet A radiation. J. Cosmet. Sci. 2016, 67, 13–20.
  49. Kalfalah, F.; Janke, L.; Schiavi, A.; Tigges, J.; Ix, A.; Ventura, N.; Boege, F.; Reinke, H. Crosstalk of clock gene expression and autophagy in aging. Aging 2016, 8, 1876–1895.
  50. Hardman, J.A.; Tobin, D.J.; Haslam, I.S.; Farjo, N.; Farjo, B.; Al-Nuaimi, Y.; Grimaldi, B.; Paus, R. The peripheral clock regulates human pigmentation. J. Investig. Dermatol. 2015, 135, 1053–1064.
  51. Slominski, A.T.; Hardeland, R.; Reiter, R. When the circadian clock meets the melanin pigmentary system. J. Investig. Dermatol. 2015, 135, 943–945.
  52. De Assis, L.V.M.; Moraes, M.N.; Mendes, D.; Silva, M.M.; Menck, C.F.M.; Castrucci, A.M.L. Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes. Curr. Issues Mol. Biol. 2021, 43, 1436–1450.
  53. Yeung, C.-Y.C.; Kadler, K.E. Chapter Eleven—Importance of the circadian clock in tendon development. In Current Topics in Developmental Biology; Olsen, B.R., Ed.; Academic Press: Cambridge, MA, USA, 2019; Volume 133, pp. 309–342.
  54. Chang, J.; Garva, R.; Pickard, A.; Yeung, C.C.; Mallikarjun, V.; Swift, J.; Holmes, D.F.; Calverley, B.; Lu, Y.; Adamson, A.; et al. Circadian control of the secretory pathway maintains collagen homeostasis. Nat. Cell Biol. 2020, 22, 74–86.
  55. Hoyle, N.P.; Seinkmane, E.; Putker, M.; Feeney, K.A.; Krogager, T.P.; Chesham, J.E.; Bray, L.K.; Thomas, J.M.; Dunn, K.; Blaikley, J.; et al. Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing. Sci. Transl. Med. 2017, 9, eaal2774.
  56. Kowalska, E.; Ripperger, J.A.; Hoegger, D.C.; Bruegger, P.; Buch, T.; Birchler, T.; Mueller, A.; Albrecht, U.; Contaldo, C.; Brown, S.A. NONO couples the circadian clock to the cell cycle. Proc. Natl. Acad. Sci. USA 2013, 110, 1592–1599.
  57. Ishii, T.; Warabi, E.; Mann, G.E. Circadian control of p75 neurotrophin receptor leads to alternate activation of Nrf2 and c-Rel to reset energy metabolism in astrocytes via brain-derived neurotrophic factor. Free Radic. Biol. Med. 2018, 119, 34–44.
  58. Ndiaye, M.A.; Nihal, M.; Wood, G.S.; Ahmad, N. Skin, reactive oxygen species, and circadian clocks. Antioxid. Redox Signal. 2014, 20, 2982–2996.
  59. Edgar, R.S.; Green, E.W.; Zhao, Y.; van Ooijen, G.; Olmedo, M.; Qin, X.; Xu, Y.; Pan, M.; Valekunja, U.K.; Feeney, K.A.; et al. Peroxiredoxins are conserved markers of circadian rhythms. Nature 2012, 485, 459–464.
  60. Avitabile, D.; Ranieri, D.; Nicolussi, A.; D’Inzeo, S.; Capriotti, A.L.; Genovese, L.; Proietti, S.; Cucina, A.; Coppa, A.; Samperi, R.; et al. Peroxiredoxin 2 nuclear levels are regulated by circadian clock synchronization in human keratinocytes. Int. J. Biochem. Cell Biol. 2014, 53, 24–34.
  61. Kolinjivadi, A.M.; Chong, S.T.; Ngeow, J. Molecular connections between circadian rhythm and genome maintenance pathways. J. Endocr.-Relat. Cancer 2021, 28, R55–R66.
  62. Kondratov, R.V.; Vykhovanets, O.; Kondratova, A.A.; Antoch, M.P. Antioxidant N-acetyl-L-cysteine ameliorates symptoms of premature aging associated with the deficiency of the circadian protein BMAL1. Aging 2009, 1, 979–987.
  63. Manzella, N.; Bracci, M.; Strafella, E.; Staffolani, S.; Ciarapica, V.; Copertaro, A.; Rapisarda, V.; Ledda, C.; Amati, M.; Valentino, M.; et al. Circadian Modulation of 8-Oxoguanine DNA Damage Repair. Sci. Rep. 2015, 5, 13752.
  64. Lyons, A.B.; Moy, L.; Moy, R.; Tung, R. Circadian Rhythm and the Skin: A Review of the Literature. J. Clin. Aesthet. Dermatol. 2019, 12, 42–45.
  65. Premi, S.; Wallisch, S.; Mano, C.M.; Weiner, A.B.; Bacchiocchi, A.; Wakamatsu, K.; Bechara, E.J.; Halaban, R.; Douki, T.; Brash, D.E. Photochemistry. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science 2015, 347, 842–847.
  66. Gaddameedhi, S.; Selby, C.P.; Kaufmann, W.K.; Smart, R.C.; Sancar, A. Control of skin cancer by the circadian rhythm. Proc. Natl. Acad. Sci. USA 2011, 108, 18790–18795.
  67. Lubov, J.E.; Cvammen, W.; Kemp, M.G. The Impact of the Circadian Clock on Skin Physiology and Cancer Development. Int. J. Mol. Sci. 2021, 22, 6112.
  68. Slominski, A.T.; Hardeland, R.; Zmijewski, M.A.; Slominski, R.M.; Reiter, R.J.; Paus, R. Melatonin: A Cutaneous Perspective on its Production, Metabolism, and Functions. J. Investig. Dermatol. 2018, 138, 490–499.
  69. Mozzanica, N.; Tadini, G.; Radaelli, A.; Negri, M.; Pigatto, P.; Morelli, M.; Frigerio, U.; Finzi, A.; Esposti, G.; Rossi, D.; et al. Plasma melatonin levels in psoriasis. Acta Derm.-Venereol. 1988, 68, 312–316.
  70. Al-Nuaimi, Y.; Hardman, J.A.; Biro, T.; Haslam, I.S.; Philpott, M.P.; Toth, B.I.; Farjo, N.; Farjo, B.; Baier, G.; Watson, R.E.B.; et al. A meeting of two chronobiological systems: Circadian proteins Period1 and BMAL1 modulate the human hair cycle clock. J. Investig. Dermatol. 2014, 134, 610–619.
  71. Cuesta, M.; Boudreau, P.; Cermakian, N.; Boivin, D.B. Skin Temperature Rhythms in Humans Respond to Changes in the Timing of Sleep and Light. J. Biol. Rhythms 2017, 32, 257–273.
  72. Schomerus, C.; Korf, H.W. Mechanisms regulating melatonin synthesis in the mammalian pineal organ. Ann. N. Y. Acad. Sci. 2005, 1057, 372–383.
  73. Kim, T.K.; Lin, Z.; Tidwell, W.J.; Li, W.; Slominski, A.T. Melatonin and its metabolites accumulate in the human epidermis in vivo and inhibit proliferation and tyrosinase activity in epidermal melanocytes in vitro. Mol. Cell. Endocrinol. 2015, 404, 1–8.
  74. Slominski, A.; Tobin, D.J.; Zmijewski, M.A.; Wortsman, J.; Paus, R. Melatonin in the skin: Synthesis, metabolism and functions. Trends Endocrinol. Metab. 2008, 19, 17–24.
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Subjects: Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Andrew Salazar
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Jörg von Hagen
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Update Date: 31 Mar 2023
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