Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis

ABSTRACT: Despite recent advances, severe acute pancreatitis (SAP) remains an extremely lethal inflammation with limited treatment options. Here, we provide compelling evidence of GV-971 (sodium oligomannate), an anti-Alzheimer's medication, as being a protective agent in various mouse SAP models. Microbiome sequencing, along with fecal microbiota transplantation and mass cytometry technology, unveiled that GV-971 reshapes the gut microbiota, increasing Faecalibacterium populations and modulating both peripheral and intestinal immune systems. A metabolomics analysis of cecal contents from GV-971–treated SAP mice further identified short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis.

ORGANISM(S): Mus musculus

PROVIDER: GSE271034 | GEO | 2024/07/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Genome-wide maps of gV sPLA2 binding sites in Raw 264.7 cells

Project description:We have searched genome-wide binding sites of mouse group V secretory phospholipase A2 (gV sPLA2) in Raw 264.7 cells. Since we previously had technical problems in immunoblotting analysis and immunoprecipitation of the gV sPLA2 protein due in part to unavailability of a specific antibody against mouse gV sPLA2 and other issues, we used a monoclonal antibody against the Myc-tag to analyze gV sPLA2 knockdown (KD) RAW 264.7 cells with re-constitutive expression of Myc-tagged gV sPLA2 or Myc-tagged gV sPLA2-H48Q, lacking catalytic activity, as well as gV sPLA2 KD RAW 264.7 cells transfected with empty vector. Among the significant peaks, the region corresponding to -375 ~ +6 from the transcriptional start site of the Pgk1 (phosphoglycerate kinase 1) gene was the strongest binding peak in the nucleus of both gV sPLA2 KD cells expressing Myc-tagged gV sPLA2 and gV sPLA2 KD cells expressing Myc-tagged gV sPLA2-H48Q. Meanwhile, the Pgk1 gene was not identified as a significant peak in the nucleus of gV sPLA2 KD cells transfected with empty vector.

2021-03-26 | GSE156528 | GEO

CircRNA expression profiles of pancreatic tissues from severe acute pancreatitis mice

Project description:Severe acute pancreatitis (SAP) is the most serious type of pancreatitis with high morbidity and mortality. The underlying mechanism behind SAP pathogenesis is complex and remains elusive. In the present study, next-generation RNA sequencing was utilized to identify circRNA transcripts in the pancreatic tissues from three SAP mice and three matched normal tissues. Our results discovered that 56 circRNAs were differently expressed in SAP compared with normal control. Our findings may provide novel insights for pathophysiological mechanism of SAP and offer novel targets for SAP.

2020-02-19 | GSE139173 | GEO

Hepatic transcriptome analysis of control, acute pancreatitis and severe acute pancreatitis mice

Project description:Purpose: The purpose of this study was to compare the hepatic transcriptome in the control group, acute pancreatitis, and severe acute pancreatitis, in order to identify metabolic gene changes during pancreatitis. Methods: 6-week Balb/c mice were subjected to AP (caerulein), SAP (caerulein and LPS) and control (saline), and mice liver tissues were harvested at 24 hours for RNA preparation (n=8 each group). Results: Among 11952 mapped genes, 8977 differentially expressed genes were identified by RNA-seq, including 351 genes induced in AP compare to Control and 5249 genes down regulated in SAP compare to AP. The genes up regulated were mainly related to fatty acid oxidation and ketone body synthesis especially Cpt2 and Acadvl, while genes that down regulated were associated with energy metabolism and inflammation. The overlap of two gene sets were 96 genes that involved in fatty acid metabolism. Conclusions: Our study revealed that in AP, genes associated with ketone body synthesis are upregulated in liver, in SAP, fatty acid oxidation related genes are downregulated in liver. Our data revealed the crosstalk between pancreas and liver, illustrated the difference of metabolism in AP and SAP.

2022-04-06 | GSE151927 | GEO

Genome-wide map of m6A circRNAs identified in mice model of severe acute pancreatitis

Project description:Severe acute pancreatitis (SAP) is the most serious type of pancreatitis with high morbidity and mortality. The underlying pathophysiological mechanism of SAP is complicated and lacking in effective therapeutic options in clinic. In recent years, circular RNAs (circRNAs) are found to be N6-methyladenosine (m6A)-modified and m6A modification of circRNAs plays important roles in physiological and pathological processes. However, the role of m6A modification of circRNAs in SAP remains unknown. Here, we aim to identify differentially expressed m6A circRNAs in SAP and to determine their biological significance and potential mechanisms in SAP. Firstly, we identified 903 m6A peaks that distribute on 781 circRNAs in SAP and control groups. Among them, 57 circRNAs with differentially expressed m6A peaks were identified, of which 32 were upregulated and 25 were downregulated. The total m6A level of circRNAs was reduced compared with control group. Moreover, the function analysis of these m6A circRNAs in SAP found that some important pathways involved in the pathogenesis of SAP, such as protein digestion and regulation of autophagy. In m6A circRNA-microRNA networks, several important miRNAs involved in the occurrence and development of SAP were found to bind to these m6A circRNAs potentially, such as miR-24-3p, miR-26a, miR-92b, miR-216b, miR-324-5p and miR-762. Notably, ALKBH5 was found to be upregulated in SAP. In conclusion, these results demonstrated that m6A modification of circRNAs was widely existed and may play important roles in the pathogenesis of SAP. Our findings provide novel insights regarding understanding the pathophysiological mechanism of SAP and seeking new therapeutic targets for SAP.

2021-11-01 | GSE173298 | GEO

Hepatic transcriptome analysis of control and severe acute pancreatitis mice

Project description:Purpose: The purpose of this study was to compare the hepatic transcriptome in the control group and severe acute pancreatitis, in order to identify metabolic gene changes during pancreatitis. Methods: 6-week Balb/c mice were subjected to control (Saline*12) and SAP (caerulein *12), and mice liver tissues were harvested at 24 hours for RNA preparation (n=6 each group). Results: Among 18257 mapped genes, 3639 differentially expressed genes were identified by RNA-seq, including 1714 genes induced in SAP compare to Control and 1892 genes down regulated in SAP compare to Control. The genes up regulated were mainly related to immune response and ER stress, while genes that down regulated were associated with fatty acids oxidation and oxidative phosphorylation. Conclusions: Our study revealed that in SAP, genes associated with immune response are upregulated in liver, fatty acid oxidation related genes are downregulated in liver. Our data revealed the crosstalk between pancreas and liver, illustrated the change of liver metabolism in SAP.

2022-04-06 | GSE183158 | GEO

Insights into microbial modulation of host peripheral lipid and glucose metabolism using mouse gut organoids

Project description:The gastrointestinal microbiota is involved in the development of various diseases, such as obesity and diabetes, by affecting nutrient acquisition, energy balance, and metabolic signaling of the host. However, the underlying mechanisms of these host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on the host epithelium using a novel gastrointestinal model based on mouse organoids. We have explored the transcriptional response of organoids upon exposure to short chain fatty acids (SCFA) and products generated by two conspicuous members of the gastrointestinal microbiota; Akkermansia muciniphila and Faecalibacterium prausnitzii. We observed that A. muciniphila metabolites affect a large variety of transcription factors and genes involved in cellular lipid metabolism and growth, supporting previous in vivo findings. F. prausnitzii products exerted only a weak effect on the host transcription profile. While, A. muciniphila, and its main metabolite propionate, both stimulate fasting-induced adipose factor/angiopoietin-like protein 4 (Fiaf/Angptl4) and Ppar? expression, important regulators of lipolysis and satiety. This work illustrates that specific members of the microbiota and their metabolites differentially modulate epithelial transcription in mouse organoid lines.

2014-07-23 | GSE59644 | GEO

Transcriptome analysis of mouse Cnot6l-/- preovulatory oocytes (GV), ovulated eggs (MII), and 1-cell zygotes

Project description:We profiled transcriptomes from Cnot6l deadenylase knock-out mouse GV oocytes, MII eggs and 1-cell zygotes in order to analyse its function during the oocyte-to-embryo (OET) transition. Transcriptome of wild-type golden hamster GV oocytes was also profiled.

2018-07-10 | GSE116771 | GEO

Microarray profiling of UPF2-deficient mouse GV oocytes.

Project description:To study the role of UPF2 during oogenesis, Upf2 was conditionally deleted in growing oocytes. Total RNA samples from UPF2-deficient GV oocytes were subjected to array profiling. The control samples for this experiment can be found in E-MTAB-5056.

2019-01-14 | E-MTAB-7064 | biostudies-arrayexpress

Quantitative proteomic analysis of both fresh and vitrified porcine GV oocytes during in vitro maturation

Project description:In this study, we used tandem mass tag (TMT)-based quantitative approach to acquire proteomic profiles of porcine GV and MII oocytes and MII oocytes vitrified at the GV stage.

2021-07-01 | PXD023107 | Pride

BAF250a Gdf9-cre knockout mice GV and MII stage oocyte transcriptome compared with control mice.

Project description:GV and MII stage oocyte transcriptome of control and BAF250aGKO mice.

2020-09-01 | GSE144658 | GEO