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Circadian Rhythm, Clock Genes and Their New Insight
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Circadian Rhythm, Clock Genes and Their New Insight

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 8823

Special Issue Editor

Dr. Fuyuki Sato

E-Mail Website
Guest Editor
Department of Diagnostic Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka Prefecture 411-8777, Japan
Interests: crosstalk between circadian rhythm and tumor progression; pathological analysis in human and mouse tissues; functional analysis of DEC1 and DEC2 in tumor progression; molecular pathways of DEC1 and DEC2; crosstalk between basic and clinical research, involving clock genes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Circadian rhythm affects human health, as well as animals, plants, and microbes. It is dominantly regulated by clock genes. Clock genes such as CLOCK, BMAL1/2, DEC1/2, PER1/2/3, and CRY1/2 play important roles in tumor progression, metabolism, immune responses, and sleep disorders by regulating apoptosis-related factors, cell cycle regulators, and inflammatory factors. On the other hand, various kinds of stress, such as hypoxia, inflammation, and anti-tumor drugs, affect the expression of clock genes. Clock genes have multiple functions that affect most living things.

Our aim is to improve the understanding of new mechanisms that circadian rhythms and clock genes affects human health, animals, plants as well as microbes, to allow the development of strategies to prevent or overcome adverse effects related to circadian rhythms. We encourage the submission of original articles, reviews and mini-reviews involving circadian rhythm, clock genes and human health, animals, plants, as well as microbes.

Topics include, but are not limited to the following:   

  • Relevant circadian rhythm/clock genes and their new insight   
  • Molecular pathways of clock genes   
  • Functional analyses of clock genes     
  • Mechanisms of circadian rhythm/clock genes-related Diseases     
  • Circadian rhythm and related drugs 

Dr. Fuyuki Sato
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • circadian rhythm
  • clock genes
  • tumor progression
  • metabolism
  • immune response
  • inflammation
  • sleep disorder
  • molecular pathway

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Published Papers (4 papers)

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16 pages, 1730 KiB  
Review
Circadian Regulation of Macrophages and Osteoclasts in Rheumatoid Arthritis
by Nobuaki Kikyo
Int. J. Mol. Sci. 2023, 24(15), 12307; https://doi.org/10.3390/ijms241512307 - 1 Aug 2023
Cited by 7 | Viewed by 2514
Abstract
Rheumatoid arthritis (RA) represents one of the best examples of circadian fluctuations in disease severity. Patients with RA experience stiffness, pain, and swelling in afflicted joints in the early morning, which tends to become milder toward the afternoon. This has been primarily explained [...] Read more.
Rheumatoid arthritis (RA) represents one of the best examples of circadian fluctuations in disease severity. Patients with RA experience stiffness, pain, and swelling in afflicted joints in the early morning, which tends to become milder toward the afternoon. This has been primarily explained by the higher blood levels of pro-inflammatory hormones and cytokines, such as melatonin, TNFα, IL-1, and IL-6, in the early morning than in the afternoon as well as insufficient levels of anti-inflammatory cortisol, which rises later in the morning. Clinical importance of the circadian regulation of RA symptoms has been demonstrated by the effectiveness of time-of-day-dependent delivery of therapeutic agents in chronotherapy. The primary inflammatory site in RA is the synovium, where increased macrophages, T cells, and synovial fibroblasts play central roles by secreting pro-inflammatory cytokines, chemokines, and enzymes to stimulate each other, additional immune cells, and osteoclasts, ultimately leading to cartilage and bone erosion. Among these central players, macrophages have been one of the prime targets for the study of the link between circadian rhythms and inflammatory activities. Gene knockout experiments of various core circadian regulators have established that disruption of any core circadian regulators results in hyper- or hypoactivation of inflammatory responses by macrophages when challenged by lipopolysaccharide and bacteria. Although these stimulations are not directly linked to RA etiology, these findings serve as a foundation for further study by providing proof of principle. On the other hand, circadian regulation of osteoclasts, downstream effectors of macrophages, remain under-explored. Nonetheless, circadian expression of the inducers of osteoclastogenesis, such as TNFα, IL-1, and IL-6, as well as the knockout phenotypes of circadian regulators in osteoclasts suggest the significance of the circadian control of osteoclast activity in the pathogenesis of RA. More detailed mechanistic understanding of the circadian regulation of macrophages and osteoclasts in the afflicted joints could add novel local therapeutic options for RA. Full article
(This article belongs to the Special Issue Circadian Rhythm, Clock Genes and Their New Insight)
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12 pages, 598 KiB  
Review
Approach to Functions of BHLHE41/DEC2 in Non-Small Lung Cancer Development
by Tatsuhiko Furukawa, Kentaro Mimami, Toshiyuki Nagata, Masatasu Yamamoto, Masami Sato and Akihide Tanimoto
Int. J. Mol. Sci. 2023, 24(14), 11731; https://doi.org/10.3390/ijms241411731 - 21 Jul 2023
Cited by 4 | Viewed by 1772
Abstract
The circadian rhythm-related genes BHLHE40/DEC1 and BHLHE41/DEC2 have various functions under different cell and tissue conditions. BHLHE41/DEC2 has been reported to be both a cancer-suppressive and an oncogenic gene during cancer development. The effects of BHLHE41/DEC2 on differentiation have been examined using Bhlhe41/Dec2 [...] Read more.
The circadian rhythm-related genes BHLHE40/DEC1 and BHLHE41/DEC2 have various functions under different cell and tissue conditions. BHLHE41/DEC2 has been reported to be both a cancer-suppressive and an oncogenic gene during cancer development. The effects of BHLHE41/DEC2 on differentiation have been examined using Bhlhe41/Dec2 knockout mice and/or in vitro differentiation models, and research has been conducted using genetic analysis of tumor cells, in vitro analysis of cancer cell lines, and immunohistochemical studies of the clinical samples. We summarize some of these studies, detail several problems, and consider possible reasons for contradictory results and the needs for further research. Full article
(This article belongs to the Special Issue Circadian Rhythm, Clock Genes and Their New Insight)
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14 pages, 809 KiB  
Review
Circadian-Coupled Genes Expression and Regulation in HIV-Associated Chronic Obstructive Pulmonary Disease (COPD) and Lung Comorbidities
by Kingshuk Panda, Srinivasan Chinnapaiyan, Md. Sohanur Rahman, Maria J. Santiago, Stephen M. Black and Hoshang J. Unwalla
Int. J. Mol. Sci. 2023, 24(11), 9140; https://doi.org/10.3390/ijms24119140 - 23 May 2023
Cited by 1 | Viewed by 2278
Abstract
People living with HIV (PLWH) have an elevated risk of chronic obstructive pulmonary disease (COPD) and are at a higher risk of asthma and worse outcomes. Even though the combination of antiretroviral therapy (cART) has significantly improved the life expectancy of HIV-infected patients, [...] Read more.
People living with HIV (PLWH) have an elevated risk of chronic obstructive pulmonary disease (COPD) and are at a higher risk of asthma and worse outcomes. Even though the combination of antiretroviral therapy (cART) has significantly improved the life expectancy of HIV-infected patients, it still shows a higher incidence of COPD in patients as young as 40 years old. Circadian rhythms are endogenous 24 h oscillations that regulate physiological processes, including immune responses. Additionally, they play a significant role in health and diseases by regulating viral replication and its corresponding immune responses. Circadian genes play an essential role in lung pathology, especially in PLWH. The dysregulation of core clock and clock output genes plays an important role in chronic inflammation and aberrant peripheral circadian rhythmicity, particularly in PLWH. In this review, we explained the mechanism underlying circadian clock dysregulation in HIV and its effects on the development and progression of COPD. Furthermore, we discussed potential therapeutic approaches to reset the peripheral molecular clocks and mitigate airway inflammation. Full article
(This article belongs to the Special Issue Circadian Rhythm, Clock Genes and Their New Insight)
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Other

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11 pages, 3074 KiB  
Brief Report
Reprogramming the Circadian Dynamics of Epileptic Genes in Mouse Temporal Lobe Epilepsy
by Sha Sun and Han Wang
Int. J. Mol. Sci. 2023, 24(7), 6400; https://doi.org/10.3390/ijms24076400 - 29 Mar 2023
Cited by 1 | Viewed by 1636
Abstract
Temporal lobe epilepsy (TLE) is a common and severe epilepsy displaying rhythmicity in humans and animals. However, how the circadian clock contributes to TLE remains elusive. A recent circadian analysis of the ventral hippocampal transcriptome of pilocarpine-induced TLE mice revealed as many as [...] Read more.
Temporal lobe epilepsy (TLE) is a common and severe epilepsy displaying rhythmicity in humans and animals. However, how the circadian clock contributes to TLE remains elusive. A recent circadian analysis of the ventral hippocampal transcriptome of pilocarpine-induced TLE mice revealed as many as 1650 rhythmically expressed transcripts. Here, a comparison of the mouse ventral hippocampal transcriptome with the human epilepsy-related gene set identified 315 possible mouse epilepsy-related genes. Rhythmicity analysis classified them into arrhythmicity, loss-of-rhythmicity, gain-of-rhythmicity, and rhythmicity-maintaining groups. KEGG and GO analyses of these mouse epilepsy genes suggest their involvement in circadian entrainment. In TLE mice, Htr1d, Drd2, and Chrna3 lose rhythmicity, but P2rx7 gains rhythmicity; the up-regulation of Htr1d and Drd2 and down-regulation of Chrna3 inhibit adenylate cyclase (AC), and up-regulation of Htr1d, Drd2, and P2rx7 activates protein kinase C (PKC). Together, these results suggest that epilepsy can disrupt the circadian dynamics of the epileptic genes, shed light on possible TLE pathogenesis, and provide potential targets for TLE diagnosis and chronotherapy. Full article
(This article belongs to the Special Issue Circadian Rhythm, Clock Genes and Their New Insight)
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