The Impact of the Circadian Clock on Skin Physiology and Cancer Development

Lubov, Janet E.; Cvammen, William; Kemp, Michael G.

doi:10.3390/ijms22116112

Cited by 29 publications

(24 citation statements)

References 123 publications

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“…There is great interest in improving the effectiveness of sunscreens to protect vulnerable individuals from mutagenesis and carcinogenesis associated with exposures to solar UV radiation, including through the use of natural products and the application of sunscreens containing DNA repair enzymes (1,2,30). Because the natural product NOB has been shown to enhance the transcriptional output of the circadian transcriptional machinery (7), which is known to regulate UV photoproduct removal and other UVB DNA damage responses (14,15,17), we investigated value of NOB in keratinocyte responses to UV radiation. Though NOB protected both HaCaT and telomerase-immortalized diploid keratinocytes from UVB radiation, we found this mechanism to be independent of DNA repair and the core circadian clock protein BMAL1.…”

Section: Discussionmentioning

confidence: 99%

The flavonoid nobiletin exhibits differential effects on cell viability in keratinocytes exposed to UVA versus UVB radiation

Cvammen

Kemp

2022

Preprint

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The polymethoxylated flavonoid nobiletin has been shown to suppress inflammatory responses to UVB radiation and to enhance circadian rhythms. Because expression of the core nucleotide excision repair (NER) factor XPA and the rate of removal of UV photoproducts from DNA are regulated by the circadian clock, we investigated whether the beneficial effects of nobiletin in UVB-exposed cells could be due in part to enhanced DNA repair. Though nobiletin limited UVB-irradiated human keratinocytes from undergoing cell death, we found that this enhanced survival was not associated with increased NER or XPA expression. Instead, nobiletin reduced initial UV photoproduct formation and promoted a G1 cell cycle arrest. We then examined the implications of this findings for exposures to solar radiation through use of a solar simulated light (SSL) source that contains primarily UVA radiation. In striking contrast to the results obtained with UVB radiation, nobiletin instead sensitized keratinocytes to both the SSL and a more defined UVA light source. This enhanced cell death was correlated with a photochemical change in nobiletin absorption spectrum in the UVA range. We conclude that nobiletin is unlikely to be a useful compound for protecting keratinocytes against the harmful effects of solar UV radiation.

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Section: Discussionmentioning

confidence: 99%

The flavonoid nobiletin exhibits differential effects on cell viability in keratinocytes exposed to UVA versus UVB radiation

Cvammen

Kemp

2022

Preprint

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“…Daily variation in gene expression have been reported in the epidermis and dermis, as well as in cutaneous and SATs and dermal hair follicles [ 38–40 ]. At the cellular level epidermal keratinocytes, hair follicle cells, dermal fibroblasts and dermal macrophages all generate rhythms on a daily timescale, as do subcutaneous adipocytes [ 41 ].…”

Section: Circadian Function In Skinmentioning

confidence: 99%

A time to heal: microRNA and circadian dynamics in cutaneous wound repair

et al. 2022

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Many biological systems have evolved circadian rhythms based on the daily cycles of daylight and darkness on Earth. Such rhythms are synchronised or entrained to 24-h cycles, predominantly by light, and disruption of the normal circadian rhythms has been linked to elevation of multiple health risks. The skin serves as a protective barrier to prevent microbial infection and maintain homoeostasis of the underlying tissue and the whole organism. However, in chronic non-healing wounds such as diabetic foot ulcers (DFUs), pressure sores, venous and arterial ulcers, a variety of factors conspire to prevent wound repair. On the other hand, keloids and hypertrophic scars arise from overactive repair mechanisms that fail to cease in a timely fashion, leading to excessive production of extracellular matrix (ECM) components such as such as collagen. Recent years have seen huge increases in our understanding of the functions of microRNAs (miRNAs) in wound repair. Concomitantly, there has been growing recognition of miRNA roles in circadian processes, either as regulators or targets of clock activity or direct responders to external circadian stimuli. In addition, miRNAs are now known to function as intercellular signalling mediators through extracellular vesicles (EVs). In this review, we explore the intersection of mechanisms by which circadian and miRNA responses interact with each other in relation to wound repair in the skin, using keratinocytes, macrophages and fibroblasts as exemplars. We highlight areas for further investigation to support the development of translational insights to support circadian medicine in the context of these cells.

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“…The circadian rhythm, or circadian clock (CC), is a hierarchically cyclic system that regulates the daily oscillations of physiological processes and can respond to external environment changes to maintain internal homeostasis [ 1 ]. Because some of these outside shifts are caused by the 24-h rotation of the Earth, and so are expected to occur approximately at the same time every day, the circadian regulation allows the human organism to anticipate these changes and synchronize them with inner physiology [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Circadian Rhythm Dysregulation and Leukemia Development: The Role of Clock Genes as Promising Biomarkers

Sanford

Cunha

Machado

et al. 2022

IJMS

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The circadian clock (CC) is a daily system that regulates the oscillations of physiological processes and can respond to the external environment in order to maintain internal homeostasis. For the functioning of the CC, the clock genes (CG) act in different metabolic pathways through the clock-controlled genes (CCG), providing cellular regulation. The CC’s interruption can result in the development of different diseases, such as neurodegenerative and metabolic disorders, as well as cancer. Leukemias correspond to a group of malignancies of the blood and bone marrow that occur when alterations in normal cellular regulatory processes cause the uncontrolled proliferation of hematopoietic stem cells. This review aimed to associate a deregulated CC with the manifestation of leukemia, looking for possible pathways involving CG and their possible role as leukemic biomarkers.

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The Impact of the Circadian Clock on Skin Physiology and Cancer Development

Cited by 29 publications

References 123 publications

The flavonoid nobiletin exhibits differential effects on cell viability in keratinocytes exposed to UVA versus UVB radiation

The flavonoid nobiletin exhibits differential effects on cell viability in keratinocytes exposed to UVA versus UVB radiation

A time to heal: microRNA and circadian dynamics in cutaneous wound repair

Circadian Rhythm Dysregulation and Leukemia Development: The Role of Clock Genes as Promising Biomarkers

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