Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of conditional deletion of Bmal1 in pancreatic β-cells in modulating transcriptional islet response to STZ-mediated pro-inflammatory injury

ABSTRACT: The circadian clock plays a vital role in modulating the cellular immune response. However, its role in mediating pro-inflammatory diabetogenic β-cell injury remains largely unexplored. Our studies demonstrate that conditional deletion of Bmal1 in mouse β-cells was shown to impair the ability of β-cells to recover from streptozotocin-mediated pro-inflammatory injury in vivo, leading to β-cell failure and the development of diabetes. Our study suggests that the β-cell circadian clock mediates β-cell response and recovery from pro-inflammatory injury common to the pathogenesis of diabetes mellitus.

ORGANISM(S): Mus musculus

PROVIDER: GSE278711 | GEO | 2024/10/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

IMPACT OF CARDIOMYOCYTE-SPECIFIC BMAL1 DELETION ON MYOCARDIAL GENE EXPRESSION, METABOLISM, AND CONTRACTILE FUNCTION

Project description:Circadian clocks are cell autonomous, transcriptionally-based, molecular mechanisms that confer the selective advantage of anticipation, enabling cells/organs to respond to environmental factors in a temporally appropriate manner. Critical to circadian clock function are two transcription factors, CLOCK and BMAL1. Previous studies in our laboratory have highlighted roles for CLOCK in cardiac physiology/pathophysiology. Here, we describe transcriptional, metabolic, and functional consequences of cardiomyocyte-specific Bmal1 knockout (CBK). Microarray analysis revealed 2037 differentially expressed genes in CBK hearts, many of which were previously identified in cardiomyocyte-specific Clock mutant (CCM) hearts. Subsequent analysis showed that Beta-hydroxybutyrate dehydrogenase 1 mRNA, protein, and enzymatic activity are markedly depressed in both CBK and CCM hearts, as is myocardial Beta-hydroxybutyrate oxidation, revealing a novel role for the circadian clock in ketone body utilization. A number of genes encoding for collagen isoforms were identified as oscillating in a time-of-day-dependent manner in wild-type, but not CBK, hearts, including col3a1, col4a1, and col4a2. Chronic induction of collagen isoform genes in CBK hearts was associated with severe age-dependent depression of cardiac function. Development of cardiomyopathy in CBK mice was associated with early mortality; all CBK mice die by one year of age. These studies highlight novel critical functions for BMAL1 in the heart, including regulation of ketone body metabolism and the extracellular matrix. RNA from whole hearts collected every 3 hours for 24 hours from wildtype and CBK mice was isolated and analyzed using MouseRef-8_V2 BeadChips (Illumina, Inc.). The 24-hour data were examined for rhythmicity using cosinor analysis and differences in rhythmicity between genotype groups were further examined for differences in the model fitting parameters.

2014-01-01 | E-GEOD-43073 | biostudies-arrayexpress

The circadian clock gene Bmal1 facilitates cisplatin-induced renal injury and hepatization

Project description:Cisplatin is one of the most potent chemotherapy drugs to treat cancers, but its clinical application remains limited due to severe nephrotoxicity. Several approaches have been developed to minimize such side effects, notably including chronotherapy, a well-known strategy based on the circadian clock. However, the component of the circadian clock machinery that particularly responses to the cisplatin stimulation remains unknown, including its functions in cisplatin-induced renal injury. In our present study, we demonstrated that Bmal1, as a key clock gene, was induced by the cisplatin stimulation in the mouse kidney and cultured human HK-2 renal cells. Gain- and loss-of-function studies indicated that Bmal1 facilitated cisplatin-induced renal injury both in vivo and in vitro, by aggravating the cell apoptotic process. More importantly, RNA-seq analysis revealed that Bmal1 triggered the expression of hallmark genes involved in renal hepatization, a critical event accompanied by the injury. At the molecular level, Bmal1 activated the transcription of hepatization-associated genes through direct recruitment to the E-box motifs of their promoters. Our findings suggest that Bmal1, a pivotal mediator induced renal injury in response to cisplatin treatment, and the therapeutic intervention targeting Bmal1 in the kidney may be a promising strategy to minimize the toxic side-effects of cisplatin in its clinical applications.

2020-04-24 | GSE149172 | GEO

IMPACT OF CARDIOMYOCYTE-SPECIFIC BMAL1 DELETION ON MYOCARDIAL GENE EXPRESSION, METABOLISM, AND CONTRACTILE FUNCTION

2014-01-01 | GSE43073 | GEO

Parathyroid tissue transcriptome over 24h of PTHcre;Bmal1 flox/flox mice and of Bmal1 flox/flox mice

Project description:The objective is to elucidate the role of the circadian clock in the parathyroid glands. We investigate the parathyroid transcriptome of wildtype mice (Bmal1 flox/flox) and of mice with parathyroid-specific excision of the circadian clock gene Bmal1 (PTHcre;Bmal1 flox/flox) harvested at 4 hour interval for 24 hours. Rhythmic genes were identified by JTK_CYCLE analysis and revealed 1455 rhythmic genes of the Bmal1 flox/flox and 1055 rhythmic genes of the PTHcre;Bmal1 flox/flox. We found global damepning of circadian clock genes with abolished rhythmicity of Cry1, Cry2, Clock, Npas2, Rorc, and Usp2. We used GSEA analysis to investigate differential expression at each timepount and found downregulation of genes involved in ATP synthesis in PTHcre;Bmal1 flox/flox mice at 4 consecutive timepoints during the active period of the mouse.

2021-12-23 | GSE191264 | GEO

RNA-sequencing of Wild-type and Bmal1 KO M1 macrophages

Project description:The goal of this study was to determine role of the circadian regulator Bmal1 in metabolic regulation in pro-inflammatory ("M1") activating by bacterial lipopolysaccharide.

2020-04-30 | GSE148510 | GEO

Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids

Project description:In mammals, circadian clocks are strictly suppressed during early embryonic stages as well as pluripotent stem cells, by the lack of CLOCK/BMAL1 mediated circadian feedback loops. During ontogenesis, the innate circadian clocks emerge gradually at a late developmental stage, then, with which the circadian temporal order is invested in each cell level throughout a body. Meanwhile, in the early developmental stage, a segmented body plan is essential for an intact developmental process and somitogenesis is controlled by another cell-autonomous oscillator, the segmentation clock, in the posterior presomitic mesoderm (PSM). In the present study, focusing upon the interaction between circadian key components and the segmentation clock, we investigated the effect of the CLOCK/BMAL1 on the segmentation clock Hes7 oscillation, revealing that the expression of functional CLOCK/BMAL1 severely interferes with the ultradian rhythm of segmentation clock in induced PSM and gastruloids. RNA sequencing analysis showed that the premature expression of CLOCK/BMAL1 affects the Hes7 transcription and its regulatory pathways. These results suggest that the suppression of CLOCK/BMAL1-mediated transcriptional regulation during the somitogenesis may be inevitable for intact mammalian development.

2021-12-09 | GSE181295 | GEO

BMAL1 Modulates Senescence Programming via AP-1 (BMAL1-ChIP-seq)

Project description:Cellular senescence and circadian dysregulation are biological hallmarks of aging. Whether they are interdependent has not been thoroughly studied. We hypothesize that BMAL1, a pioneer transcription factor and master regulator of the molecular circadian clock, plays a role in the senescence program. In this study, we show that BMAL1 in is uniquely localized to genomic motifs associated with AP-1 in senescent cells and contributes to AP-1 transcriptional control of the senescence program.

2023-08-22 | GSE229009 | GEO

Transcriptional Repressor Gm129 Modulates the Circadian Gene Expression by Inhibiting CLOCK:BMAL1 Activity

Project description:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK-BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK:BMAL1:CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized protein that directly interacts with BMAL1 and represses CLOCK:BMAL1 activity. In vitro and in vivo protein-DNA interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK:BMAL1 complex on DNA. Although Gm129-/- or Cry1-/- Gm129-/- mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit significant phase delay compared to control. Our results suggest that, in addition to CRYs and PERs, GM129 protein contributes to the transcriptional feedback loop by modulating CLOCK:BMAL1 activity as a transcriptional repressor. Examination of 3 transcriptional regulators in mouse liver

2014-01-07 | E-GEOD-53828 | biostudies-arrayexpress

Effect of conditional deletion of Bmal1 in pancreatic β-cells in modulating transcriptional islet response to STZ-mediated pro-inflammatory injury

Project description:Effect of conditional deletion of Bmal1 in pancreatic β-cells in modulating transcriptional islet response to STZ-mediated pro-inflammatory injury

| PRJNA1168494 | ENA

Diurnal profiling of mouse liver of hepatocyte specific BMAL1 KO mice (Bmal1 HepKO)

Project description:Obesity and liver diseases are associated with the disruption of the circadian clock that orchestrates mammalian physiology to optimize nutrient metabolism and storage. We show here that the activity of the circadian clock regulator BMAL1 is perturbed during liver fibrosis in humans. To understand the impact of BMAL1 perturbation in obesity and liver diseases, we assessed the impact of a high fat diet or leptin deficiency on Bmal1 knockout mice. While Bmal1 knockout mice were prone to obesity, they were protected against insulin resistance, hepatic steatosis, inflammation, and fibrosis. In addition to direct transcriptional regulation of metabolic programs by BMAL1, we show that adaptation of the growth hormone and sex hormone pathways plays a critical role in this protection. Similar endocrine perturbations correlate with the development of liver fibrosis in humans, suggesting that endocrine perturbation associated with circadian disruption is critical for the pathogenesis of metabolic and liver diseases.

2022-01-26 | GSE190221 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data