Regulation of Circadian Rhythm of Human Vascular Endothelial Growth Factor by Circadian Rhythm of Hypoxia Inducible Factor-1α : Implication for Clinical Use as Anti-Angiogenic Therapy

Fujita, Shotaro; Koyama, Yoshihisa; Higashimoto, Masashi; Ono, Kazuhisa; Ono, Tomojiro; Watanabe, Kenji; Yoshimoto, Nobuhiro; Momma, Tomoyuki; Saito, Masaru; Sugeno, Hidekazu; Sassa, Motoki; Ishigame, Teruhide; Sakamoto, Wataru; Abe, Noriko; Yazawa, Takashi; Miyamoto, K.; Tachibana, Kazunoshin; Iwadate, Manabu; Ohtake, Toru; Takebayashi, Yuji; Takenoshita, Seiichi

doi:10.4993/acrt.18.28

Cited by 6 publications

(6 citation statements)

References 41 publications

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“…These in turn downregulate their own expression and allow for a new cycle of the feedback loop with a period of approximately 24 h (Idda et al 2012). Among the transcripts evidencing a rhythmic, circadian expression pattern, several genes were identified that are also known to be under the control of the hypoxic signaling pathway, such as, for example, erythropoietin (epo) and vascular endothelial growth factor (vegf; Bozek et al 2009;Fujita et al 2010;Jensen et al 2012). In normoxic zebrafish the mRNA expression of epo and veg f165 also underlies a diurnal expression pattern; epo mRNA, for example, is mostly produced during the night phase.…”

Section: Influence Of Circadian Rhythms On Hif Expressionmentioning

confidence: 99%

Multiplicity of Hypoxia-Inducible Transcription Factors and Their Connection to the Circadian Clock in the Zebrafish

Pelster

Egg

2015

Physiological and Biochemical Zoology

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In zebrafish, as in most vertebrates, three different isoforms of the hypoxia-inducible transcription factor, Hif-1α, Hif-2α, and Hif-3α, have been identified. The expression data of genes encoding these three proteins, as analyzed so far, show distinct expression patterns for all three isoforms during early development, under hypoxic conditions, and during exercise, suggesting differential roles for all three proteins under these different conditions. While isoform-specific functions for Hif-1α and Hif-2α have been identified in recent years, the role of Hif-3α remains somewhat elusive. Several studies mostly using mammalian cells or tissues discussed Hif-3α as a competitive inhibitor of Hif-1α and Hif-2α. In zebrafish, the expression changes for Hif-1α and Hif-3α observed during development and under environmental stress conditions do not support this hypothesis, and recent studies indicate that Hif-3α is also able to directly control transcriptional activity of certain genes. The Hif signaling pathway is tightly connected to cell circuitries such as glucose and lipid metabolism, and only very recently a further linkage to the circadian clock has been described. In this context a detailed analysis of the mRNA concentrations of hif-1α, hif-2α, and hif-3α also revealed a circadian expression pattern for hif-3α mRNA under normoxic conditions in zebrafish larvae. In addition, accumulation of Hif-1α protein during short-term hypoxia was found to depend on the time within the daily light and dark cycle at which hypoxia was encountered, suggesting that the hypoxia signaling pathway may be regulated by the circadian clock. This is supported by the fact that some of the downstream genes of the Hif signaling pathway, namely, erythropoietin and vascular endothelial growth factor, are known to be clock controlled as well. Furthermore, in developing zebrafish, the disruption of the circadian rhythm was shown to result in a diminished hypoxic response with a modified life cycle of erythrocytes and an altered patterning of the vascular bed, leading to even higher mortality rates of chronodisrupted animals. Hif protein, in turn, is known to affect the circadian clock pathway in zebrafish. Previously, we demonstrated that Hif-1α directly binds to defined E-boxes of the period 1 gene, leading to a sustained dampening of its oscillation amplitude. Here we show that Hif-1α also binds to the promoter of the period 2 gene, indicating that multiple connections between the Hif signaling pathway and the circadian clock exist. The redundancy of the coupling between both pathways might be evidence for the coevolution of both circuits after the great oxygenation event about 2.5 billion years ago. Coupling the circadian clock and the hypoxic signaling pathway may have conferred selective advantages by facilitating a coordinated response of cells and organisms to alternating day-night cycles and concomitant variable food availabilities in the face of varying oxygen supply.

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Section: Influence Of Circadian Rhythms On Hif Expressionmentioning

confidence: 99%

Multiplicity of Hypoxia-Inducible Transcription Factors and Their Connection to the Circadian Clock in the Zebrafish

Pelster

Egg

2015

Physiological and Biochemical Zoology

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“…In mammals, HIF‐1 has been described as a factor with overrepresented binding sites in the promoters of clock‐controlled genes (CCGs) (23), and an HIF‐1‐dependent circadian rhythm has been recently reported with respect to mRNA and promoter activity in human cells (24). Although we did not measure the HIF‐1α circadian variations in the current study, the differences between the HIF‐1α abundance at 08:00 and 20:00 under all of the experimental conditions (although the differences were not statistically significant because of the high standard errors), and particularly under DD, suggest an HIF‐1α circadian rhythm in the central oscillators of crayfish.…”

Section: Discussionmentioning

confidence: 99%

Daily Light–Dark Cycles Influence Hypoxia‐Inducible Factor 1 and Heat Shock Protein Levels in the Pacemakers of Crayfish

Velázque‐Amado

Escamilla‐Chimal

Fanjul‐Moles

2011

Photochem & Photobiology

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It has been proposed that at moderate concentrations, reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses, such as those mediated by the glutathione (GSH) system, protect cells against oxidative stress and reestablish "redox homeostasis." The response to stress is controlled by specific transcription factors, such as hypoxia-inducible factor 1 (HIF-1), which interacts with chaperones such as heat shock proteins (HSP) that stabilize intracellular components. We have reported that the oxidation produced by extreme light cycles was coupled to cellular fluctuations in the production of free radicals and ROS in crayfish. Herein, we investigated whether ROS resulting from light-dark cycles (20:4 LD) with a long photoperiod activated HIF-1α in the putative pacemakers of crayfish. Our results indicate that both the light resulting from equatorial and extreme daily light cycles and the constant darkness-induced HIF-1α and heat shock protein 70 (HSP70) appeared to regulate each other. The interaction between these proteins and the ability of crayfish to shift from the oxidative to glycolytic pathways, thereby synchronizing to extreme illumination conditions and maintaining a rhythmic predictive relationship with the environment, suggest HIF-1 as a key factor in these rhythmic metabolic interactions.

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“…While it has not been demonstrated that the disruption in BMAL1 signalling is the cause of ischaemia‐induced angiogenesis, these findings suggest that ROR‐α may be a negative regulator of ischaemia‐induced angiogenesis 83 . The regulation of VEGF‐A mRNA and VEGF‐A protein expression levels by the circadian fluctuations of HIF‐α has been confirmed in a human colon cancer cell line following serum shock 84 . Indeed, studies using human cell lines identified BMAL2 and CLOCK as key regulators of VEGF‐A, with levels of VEGF‐A peaking during the night 85,86 .…”

Section: Exploiting the Circadian Clock To Personalised Anti‐angiogen...mentioning

confidence: 94%

“…83 The regulation of VEGF-A mRNA and VEGF-A protein expression levels by the circadian fluctuations of HIFα has been confirmed in a human colon cancer cell line following serum shock. 84 Indeed, studies using human cell lines identified BMAL2 and CLOCK…”

Section: E Xploiting the Circ Ad Ian Clo Ck To Per Sonalis Ed Anti -A...mentioning

confidence: 99%

Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management

Luengas‐Martinez

Paus

Iqbal

et al. 2022

Experimental Dermatology

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The physiology and pathology of the skin are influenced by daily oscillations driven by a master clock located in the brain, and peripheral clocks in individual cells. The pathogenesis of psoriasis is circadian‐rhythmic, with flares of disease and symptoms such as itch typically being worse in the evening/night‐time. Patients with psoriasis have changes in circadian oscillations of blood pressure and heart rate, supporting wider circadian disruption. In addition, shift work, a circadian misalignment challenge, is associated with psoriasis. These features may be due to underlying circadian control of key effector elements known to be relevant in psoriasis such as cell cycle, proliferation, apoptosis and inflammation. Indeed, peripheral clock pathology may lead to hyperproliferation of keratinocytes in the basal layers, insufficient apoptosis of differentiating keratinocytes in psoriatic epidermis, dysregulation of skin‐resident and migratory immune cells and modulation of angiogenesis through circadian oscillation of vascular endothelial growth factor A (VEGF‐A) in epidermal keratinocytes. Chronotherapeutic effects of topical steroids and topical vitamin D analogues have been reported, suggesting that knowledge of circadian phase may improve the efficacy, and therapeutic index of treatments for psoriasis. In this viewpoint essay, we review the current literature on circadian disruption in psoriasis. We explore the hypothesis that psoriasis is circadian‐driven. We also suggest that investigation of the circadian components specific to psoriasis and that the in vitro investigation of circadian regulation of psoriasis will contribute to the development of a novel chronotherapeutic treatment strategy for personalised psoriasis management. We also propose that circadian oscillations of VEGF‐A offer an opportunity to enhance the efficacy and tolerability of a novel anti‐VEGF‐A therapeutic approach, through the timed delivery of anti‐VEGF‐A drugs.

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Regulation of Circadian Rhythm of Human Vascular Endothelial Growth Factor by Circadian Rhythm of Hypoxia Inducible Factor-1α : Implication for Clinical Use as Anti-Angiogenic Therapy

Cited by 6 publications

References 41 publications

Multiplicity of Hypoxia-Inducible Transcription Factors and Their Connection to the Circadian Clock in the Zebrafish

Multiplicity of Hypoxia-Inducible Transcription Factors and Their Connection to the Circadian Clock in the Zebrafish

Daily Light–Dark Cycles Influence Hypoxia‐Inducible Factor 1 and Heat Shock Protein Levels in the Pacemakers of Crayfish

Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management

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