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Hepatocyte SREBP signaling mediates clock communication within the liver

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE206319 | GEO | 2023/04/03

REPOSITORIES: GEO

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Hepatocyte SREBP signaling mediates clock communication within the liver [ATAC-seq]

Project description:Rhythmic intraorgan communication coordinates environmental signals and cell-intrinsic clock to maintain organ homeostasis. Hepatocyte-specific knockout of core components of the molecular clock, Rev-erba and b (ReverbhDKO), alters cholesterol and lipid metabolism in hepatocytes as well as rhythmic gene expression in non-parenchymal cells (NPC) of the liver. Here we report that in diet induced obesity (DIO)-caused fatty liver, hepatocyte SREBP cleavage-activating protein (SCAP) is required for ReverbhDKO-induced diurnal rhythmic remodeling and epigenomic reprogramming in Kupffer cells (KC). Integrative analyses of isolated hepatocytes and Kupffer cells uncovered potential signals, including secreted polypeptides and metabolites, that gain rhythmicity in the absence of REV-ERBs in a SCAP-dependent manner. These results shed light on the signaling mechanisms by which hepatocytes regulate diurnal rhythms in NPCs in DIO and fatty liver disease.

2023-04-04 | GSE206318 | GEO

Hepatocyte SREBP signaling mediates clock communication within the liver [scRNA-seq]

2023-04-04 | GSE206317 | GEO

Hepatocyte SREBP signaling mediates clock communication within the liver [RNA-seq]

2023-04-04 | GSE206316 | GEO

The Autonomous Hepatocyte Clock Controls Acetaminophen Bioactivation and Chronotoxicity

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-08-30 | E-GEOD-34444 | biostudies-arrayexpress

The hepatocyte clock and feeding control chronophysiology of multiple liver cell types

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-07-30 | GSE143528 | GEO

The hepatocyte insulin receptor is required to program rhythmic gene expression and the liver clock

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-01-01 | GSE165156 | GEO

The Autonomous Hepatocyte Clock Controls Acetaminophen Bioactivation and Chronotoxicity

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-08-30 | GSE34444 | GEO

IL-17/CXCL5 signaling within the oligovascular niche mediates human and mouse white matter injury

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-11-11 | GSE217356 | GEO

Long Noncoding RNA Inhibits Hepatocyte Proliferation during Liver Regeneration

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-06-26 | E-GEOD-70343 | biostudies-arrayexpress

Clock mediates liver senescence by controlling ER stress.

Project description:Accumulated evidence indicates that circadian genes regulate cell damage and senescence in most mammals. Endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) regulate longevity in many organisms. However, the specific mechanisms of the relationship between the circadian clock and the two stress processes in organisms are poorly understood. Here, we show that Clock-mediated Pdia3 expression is required to sustain reactive oxidative reagents and ER stress. First, ER stress and ROS are strongly activated in the liver tissue of Clock?19 mutant mice, which exhibit a significant aging phenotype. Next, transcription of Pdia3 is mediated by the circadian gene Clock, but this process is affected by the Clock?19 mutant due to the low affinity of the E-box motif in the promoter. Finally, ablation of Pdia3 with siRNA causes ER stress with sustained phosphorylation of PERK and eIF1?, resulting in exaggerated up-regulation of UPR target genes and increased apoptosis as well as ROS. Moreover, the combined effects result in an imbalance of cell homeostasis and ultimately lead to cell damage and senescence. Taken together, this study identified the circadian gene Clock as a regulator of ER stress and senescence, which will provide a reference for the clinical prevention of aging.

| S-EPMC5764397 | biostudies-literature

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