REV-ERBα Agonist GSK4112 attenuates Fas-induced Acute Hepatic Damage in Mice

Shao, Ruyue; Yang, Yongqiang; Fan, Kerui; Wu, Xicheng; Jiang, Rong; Tang, Li; Li, Longjiang; Shen, Yi; Liu, Gang; Zhang, Li

doi:10.7150/ijms.52011

Cited by 5 publications

(6 citation statements)

References 42 publications

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“…–Inhibition of hepatocyte apoptosis, with a reduction of caspase-3 and caspase-8 activities. Wild-type and Jo2 treated C57BL/6 mice Liver injury 149 –Inhibition of LPS-induced phosphorylation of IκK, thereby blocking p65 nuclear translocation and suppressing the expression of proinflammatory cytokines, such as IL-6 and TNFα. BV2 cells and Male C57BL/6 mice Neuro-inflammation; neurodegenerative diseases; psychiatric disorders 150 –Protection of ventral midbrain neurons from LPS-induced microglial activation-induced damage.…”

Section: Time As a Crucial Dimension To Medicinementioning

confidence: 99%

Molecular regulations of circadian rhythm and implications for physiology and diseases

Fagiani

Marino

Romagnoli

et al. 2022

Sig Transduct Target Ther

130

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The term “circadian rhythms” describes endogenous oscillations with ca. 24-h period associated with the earth’s daily rotation and light/dark cycle. Such rhythms reflect the existence of an intrinsic circadian clock that temporally orchestrates physiological processes to adapt the internal environment with the external cues. At the molecular level, the circadian clock consists of multiple sets of transcription factors resulting in autoregulatory transcription-translation feedback loops. Notably, in addition to their primary role as generator of circadian rhythm, the biological clock plays a key role in controlling physiological functions of almost all tissues and organs. It regulates several intracellular signaling pathways, ranging from cell proliferation, DNA damage repair and response, angiogenesis, metabolic and redox homeostasis, to inflammatory and immune response. In this review, we summarize findings showing the crosstalk between the circadian molecular clock and some key intracellular pathways, describing a scenario wherein their reciprocal regulation impinges upon several aspects of mammalian physiology. Moreover, based on evidence indicating that circadian rhythms can be challenged by environmental factors, social behaviors, as well as pre-existing pathological conditions, we discuss implications of circadian misalignment in human pathologies, such as cancer and inflammatory diseases. Accordingly, disruption of circadian rhythm has been reported to affect several physiological processes that are relevant to human diseases. Expanding our understanding of this field represents an intriguing and transversal medicine challenge in order to establish a circadian precision medicine.

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Section: Time As a Crucial Dimension To Medicinementioning

confidence: 99%

Molecular regulations of circadian rhythm and implications for physiology and diseases

Fagiani

Marino

Romagnoli

et al. 2022

Sig Transduct Target Ther

130

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“…Fas receptor (CD95), a member of the TNF-receptor superfamily with a death domain, mediates the assembly of a death-inducing signaling complex. Inducing caspase activation and cell apoptosis ( 219 ) has been considered the critical mechanism of fulminant liver failure ( 220 ), ischaemia-reperfusion-associated liver diseases ( 221 ), nonalcoholic fatty liver disorders ( 222 ) and other acute and chronic hepatic disorders. The liver constitutively and abundantly expresses the Fas receptor and activated caspase (casp) 8 upon binding of FasL or other receptor agonists ( 220 , 223 ), such as the Fas receptor antibody JO2 and soluble FasL in the hexameric form (MegaFasL) ( 198 ).…”

Section: Developing Animal Models Of Liver Failure and The Mechanism ...mentioning

confidence: 99%

“…Inducing caspase activation and cell apoptosis ( 219 ) has been considered the critical mechanism of fulminant liver failure ( 220 ), ischaemia-reperfusion-associated liver diseases ( 221 ), nonalcoholic fatty liver disorders ( 222 ) and other acute and chronic hepatic disorders. The liver constitutively and abundantly expresses the Fas receptor and activated caspase (casp) 8 upon binding of FasL or other receptor agonists ( 220 , 223 ), such as the Fas receptor antibody JO2 and soluble FasL in the hexameric form (MegaFasL) ( 198 ). Then, it triggers the caspase cascade accompanied by excessive hepatocyte apoptosis ( 224 ), which can quickly progress to secondary necrosis ( 225 ).…”

Section: Developing Animal Models Of Liver Failure and The Mechanism ...mentioning

confidence: 99%

“…Several researchers have reported that JO2 at concentrations such as 0.15, 0.2, 0.23, 0.35, 0.4, 0.42, and 0.5 mg/kg can induce liver failure, and the severity of liver injury is dependent on the JO2 dose ( 220 , 221 , 225 – 231 ). Thus, the critical element for developing this animal model is the concentration of JO2.…”

Section: Developing Animal Models Of Liver Failure and The Mechanism ...mentioning

confidence: 99%

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Isolation, culture, and delivery considerations for the use of mesenchymal stem cells in potential therapies for acute liver failure

Yang,

Chen,

2023

Front. Immunol.

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Acute liver failure (ALF) is a high-mortality syndrome for which liver transplantation is considered the only effective treatment option. A shortage of donor organs, high costs and surgical complications associated with immune rejection constrain the therapeutic effects of liver transplantation. Recently, mesenchymal stem cell (MSC) therapy was recognized as an alternative strategy for liver transplantation. Bone marrow mesenchymal stem cells (BMSCs) have been used in clinical trials of several liver diseases due to their ease of acquisition, strong proliferation ability, multipotent differentiation, homing to the lesion site, low immunogenicity and anti-inflammatory and antifibrotic effects. In this review, we comprehensively summarized the harvest and culture expansion strategies for BMSCs, the development of animal models of ALF of different aetiologies, the critical mechanisms of BMSC therapy for ALF and the challenge of clinical application.

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“…An important mechanism of hepatocyte damage during acute and chronic hepatic diseases, such as virus-driven hepatitis, ALD, NAFLD, and ischemia/reperfusion (I/R)-induced liver injury, is the aberrant activation of apoptosis by Fas (a death receptor also known as CD95). Fortunately, treatment with GSK4112 improves liver damage caused by Fas in mice [ 67 ]. Mechanistically, GSK4112 reduces Fas levels, enhances Akt phosphorylation, and lowers caspase-3 and caspase-8 activity, thereby inhibiting hepatocyte apoptosis and ameliorating liver injury.…”

Section: Physiological and Pathological Roles Of Nr1d1 In Various Organsmentioning

confidence: 99%

Targeting NR1D1 in organ injury: challenges and prospects

Zhang-sun,

Xu,

Escames

et al. 2023

Military Med Res

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Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα) belongs to the nuclear receptor (NR) family, and is a heme-binding component of the circadian clock that consolidates circadian oscillators. In addition to repressing the transcription of multiple clock genes associated with circadian rhythms, NR1D1 has a wide range of downstream target genes that are intimately involved in many physiopathological processes, including autophagy, immunity, inflammation, metabolism and aging in multiple organs. This review focuses on the pivotal role of NR1D1 as a key transcription factor in the gene regulatory network, with particular emphasis on the milestones of the latest discoveries of NR1D1 ligands. NR1D1 is considered as a promising drug target for treating diverse diseases and may contribute to research on innovative biomarkers and therapeutic targets for organ injury-related diseases. Further research on NR1D1 ligands in prospective human trials may pave the way for their clinical application in many organ injury-related disorders.

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REV-ERBα Agonist GSK4112 attenuates Fas-induced Acute Hepatic Damage in Mice

Cited by 5 publications

References 42 publications

Molecular regulations of circadian rhythm and implications for physiology and diseases

Molecular regulations of circadian rhythm and implications for physiology and diseases

Isolation, culture, and delivery considerations for the use of mesenchymal stem cells in potential therapies for acute liver failure

Targeting NR1D1 in organ injury: challenges and prospects

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