Circadian transcriptome analysis in human fibroblasts from Hunter syndrome and impact of iduronate-2-sulfatase treatment

Mazzoccoli, Gianluigi; Tomanin, Rosella; Mazza, Tommaso; D’Avanzo, Francesca; Salvalaio, Marika; Rigon, Laura; Zanetti, Alessandra; Pazienza, Valerio; Francavilla, M.; Giuliani, Francesco; Vinciguerra, Manlio; Scarpa, Maurizio

doi:10.1186/1755-8794-6-37

Cited by 15 publications

(10 citation statements)

References 61 publications

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“…Nr1d1 and nr1d2 were identified as the constitutive transcriptional repressors of arntl1 , whereas rorα is the arntl1 transcriptional activator [2, 41]. In addition, nr1d1 was considered to be interwoven into the core clock mechanism via downregulating the clock expression.…”

Section: Discussionmentioning

confidence: 99%

Daily rhythmicity of clock gene transcript levels in fast and slow muscle fibers from Chinese perch (Siniperca chuatsi)

Cheng

et al. 2016

BMC Genomics

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BackgroundClock genes are considered to be the molecular core of biological clock in vertebrates and they are directly involved in the regulation of daily rhythms in vertebrate tissues such as skeletal muscles. Fish myotomes are composed of anatomically segregated fast and slow muscle fibers that possess different metabolic and contractile properties. To date, there is no report on the characterization of the circadian clock system components of slow muscles in fish.ResultsIn the present study, the molecular clock components (clock, arntl1/2, cry1/2/3, cry-dash, npas2, nr1d1/2, per1/2/3, rorα and tim genes) and their daily transcription levels were characterized in slow and fast muscles of Chinese perch (Siniperca chuatsi). Among the 15 clock genes, nrld2 and per3 had no daily rhythmicity in slow muscles, and cry2/3 and tim displayed no daily rhythmicity in fast muscles of the adult fish. In the slow muscles, the highest expression of the most clock paralogs occurred at the dark period except arntl1, nr1d1, nr1d2 and tim. With the exception of nr1d2 and tim, the other clock genes had an acrophase at the light period in fast muscles. The circadian expression of the myogenic regulatory factors (mrf4 and myf5), mstn and pnca showed either a positive or a negative correlation with the transcription pattern of the clock genes in both types of muscles.ConclusionsIt was the first report to unravel the molecular clock components of the slow and fast muscles in vertebrates. The expressional pattern differences of the clock genes between the two types of muscle fibers suggest that the clock system may play key roles on muscle type-specific tissue maintenance and function.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3373-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Daily rhythmicity of clock gene transcript levels in fast and slow muscle fibers from Chinese perch (Siniperca chuatsi)

Cheng

et al. 2016

BMC Genomics

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“…The use of fibroblasts from MPS II patients and healthy controls allowed basic affected mechanisms to be dissected. Mazzoccoli and colleagues demonstrated the altered expression of clock genes and clock-controlled genes, suggesting their possible involvement in the deregulation of cellular homeostasis and therefore in the pathophysiology of the disease [207]. Recently, Moskot and co-workers demonstrated a cell cycle block of MPS II cells in the G0/G1 phase, compared to healthy controls, and a partial capability of genistein to rescue these cell cycle disturbances [191].…”

Section: Cell Modelsmentioning

confidence: 99%

Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

D’Avanzo

Rigon

Zanetti

et al. 2020

IJMS

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102

145

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Mucopolysaccharidosis type II (MPS II, Hunter syndrome) was first described by Dr. Charles Hunter in 1917. Since then, about one hundred years have passed and Hunter syndrome, although at first neglected for a few decades and afterwards mistaken for a long time for the similar disorder Hurler syndrome, has been clearly distinguished as a specific disease since 1978, when the distinct genetic causes of the two disorders were finally identified. MPS II is a rare genetic disorder, recently described as presenting an incidence rate ranging from 0.38 to 1.09 per 100,000 live male births, and it is the only X-linked-inherited mucopolysaccharidosis. The complex disease is due to a deficit of the lysosomal hydrolase iduronate 2-sulphatase, which is a crucial enzyme in the stepwise degradation of heparan and dermatan sulphate. This contributes to a heavy clinical phenotype involving most organ-systems, including the brain, in at least two-thirds of cases. In this review, we will summarize the history of the disease during this century through clinical and laboratory evaluations that allowed its definition, its correct diagnosis, a partial comprehension of its pathogenesis, and the proposition of therapeutic protocols. We will also highlight the main open issues related to the possible inclusion of MPS II in newborn screenings, the comprehension of brain pathogenesis, and treatment of the neurological compartment.

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“…Besides, a semantic hypergraph-based analysis highlighted five gene clusters significantly associated to important biological processes or pathways and five genes, AHR, HIF1A, CRY1, ITGA5, and EIF2B3, proven to be central players in these pathways. The results imply a decisive contribution of deregul a t i o n o f t h e c l o c k g e n e m a c h i n e r y i n t h e pathophysiological mechanisms underlying the derangement of cellular processes as well as the alteration of tissue function and anatomical integrity that hallmark the organ systems involved in the patients affected by Hunter syndrome (Mazzoccoli et al 2013). More importantly, only circadian genes when mutated appear to be responsible of the altered lysosomal function and resulting anatomical and functional derangements that hallmark the LSDs.…”

Section: The Molecular Clockwork and Circadian Rhythmicity In Lsdsmentioning

confidence: 90%

“…Considering that the biological clock drives processes that are crucial for the maintenance of body homeostasis, it is tempting to speculate on the involvement of the circadian clock circuitry in the pathophysiological mechanism underlying these diseases. In line with this hypothesis, a severe deregulation of expression of clock genes and clock-controlled genes has been evidenced in a study that evaluated by whole transcriptome analysis through next-generation sequencing the expression of circadian genes in normal primary human fibroblasts and compared it to the circadian transcriptome of fibroblasts obtained from Hunter syndrome patients before and 24 h/ 144 h after iduronate-2-sulfatase treatment in vitro and evaluated also by qRT-PCR the time-related expression of core clock genes before and after 24 h of iduronate-2sulfatase treatment upon synchronization by serum shock (Mazzoccoli et al 2013). The expression of several core clock genes and clock-controlled genes was distorted and showed dynamic modifications 24 and 144 h after iduronate-2-sulfatase treatment.…”

Section: The Molecular Clockwork and Circadian Rhythmicity In Lsdsmentioning

confidence: 99%

The Biological Clock and the Molecular Basis of Lysosomal Storage Diseases

et al. 2014

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The lysosomal storage disorders encompass nearly fifty diseases provoked by lack or deficiency of enzymes essential for the breakdown of complex molecules and hallmarked by accumulation in the lysosomes of metabolic residues. Histochemistry and cytochemistry studies evidenced patterns of circadian variation of the lysosomal marker enzymes, suggesting that lysosomal function oscillates rhythmically during the 24-h day. The circadian rhythmicity of cellular processes is driven by the biological clock ticking through transcriptional/translational feedback loops hardwired by circadian genes and proteins. Malfunction of the molecular clockwork may provoke severe deregulation of downstream gene expression regulating a complex array of cellular functions leading to anatomical and functional changes. In this review we highlight that all the genes mutated in lysosomal storage disorders encode circadian transcripts suggesting a direct participation of the biological clock in the pathophysiological mechanisms underlying cellular and tissue derangements hallmarking these hereditary diseases. The 24-h periodicity of oscillation of gene transcription and translation could lead in physiological conditions to circadian rhythmicity of fluctuation of enzyme levels and activity, so that gene transfer could be envisaged to reproduce 24-h periodicity of variation of enzymatic dynamics and circadian rhythmicity could have an impact on the schedule of enzyme replacement therapy.

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Circadian transcriptome analysis in human fibroblasts from Hunter syndrome and impact of iduronate-2-sulfatase treatment

Cited by 15 publications

References 61 publications

Daily rhythmicity of clock gene transcript levels in fast and slow muscle fibers from Chinese perch (Siniperca chuatsi)

Daily rhythmicity of clock gene transcript levels in fast and slow muscle fibers from Chinese perch (Siniperca chuatsi)

Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

The Biological Clock and the Molecular Basis of Lysosomal Storage Diseases

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