ACSS2 alleviates alcoholic liver disease via modulating hepcidin-mediated systemic iron homeostasis and hepatic ferroptosis
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ABSTRACT:
PROVIDER: PRJNA1112313 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29051629_1.fastq.gz | Fastqsanger.gz | |||
| SRR29051629_2.fastq.gz | Fastqsanger.gz | |||
| SRR29051630_1.fastq.gz | Fastqsanger.gz | |||
| SRR29051630_2.fastq.gz | Fastqsanger.gz | |||
| SRR29051631_1.fastq.gz | Fastqsanger.gz |
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Project description:Alcoholic liver disease (ALD) is one of the most prevalent types of liver disease associated with high morbidity and mortality, caused by hepatotoxicity originating from alcohol metabolism, but current therapeutic drugs are still limited. The role of ACSS2 as an enzyme that metabolizes acetate in ALD remains unknown. Our study aimed to investigate the function of ACSS2 and its potential mechanism in ALD progression.
2024-08-28 | GSE267638 | GEO
Project description:Quantification and characterisation of canine hepcidin by LC-MS
2020-05-26 | PXD015661 | Pride
Project description:Bleeding and altered iron distribution occur in multiple gastrointestinal diseases, but the significance or regulation of these changes remains unclear. Here we report that hepcidin, the master regulator of systemic iron homeostasis, is required for tissue repair in the intestine following experimental damage. This effect was independent of hepatocyte-derived hepcidin or systemic iron levels. Rather, we identified that conventional dendritic cells (DCs) are a source of hepcidin that is induced by microbial stimulation, prominent in the inflamed intestine of humans, and essential for tissue repair. Mechanistically, DC-derived hepcidin acted on ferroportin-expressing phagocytes to promote local iron sequestration, which regulated the microbiota and subsequently facilitated intestinal repair. Collectively, these results identify a novel pathway whereby DC-derived hepcidin promotes mucosal healing in the intestine via nutritional immunity.
2020-04-15 | GSE139371 | GEO
Project description:Liver iron overload can induce hepatic expression of hepcidin and regulates iron metabolism. However, the mechanism of iron regulating iron metabolism remains known. Intracellular labile iron represents the nonferritin-bound, redox-active iron which is transitory and serves as a crossroad of cell iron metabolism. The role of intracellular labile iron played in iron metabolism has largely been elucidated. Here we show that intracellular labile iron of hepatocytes has dual function in iron metabolism. It can induce hepatocytes expressing hepcidin via ER stress induced transcription factors on the one hand, on the other hand stimulate BMP2 and BMP6 expression of liver sinusoidal endothelial cells (LSECs) though TNFα secreted by hepatocytes to further regulate iron metabolism. Blockade of TNFα could dysregulate the iron metabolism during iron overload. Our findings reveal the important role of intracellular labile iron in iron metabolism and represent a novel way to modulate iron metabolism during iron overload.
2023-05-03 | GSE186655 | GEO
Project description:Iron-related disorders are among the most prevalent diseases worldwide. Systemic iron homeostasis requires hepcidin (Hamp), a hepatic-derived hormone that controls iron mobilization through its molecular target, ferroportin (FPN), the only known mammalian iron exporter. Here, we took a transcriptomic approach to to compare the duodenal transcriptome during systemic iron demand to that of hepcidin-deficiency iron overload. Hampfl/fl (control) and AlbCreERT2;Hampfl/fl mice were placed on iron-replete and low-iron diets and were sacrificed two weeks following tamoxifen treatment. Duodenum RNA expression was compared across genotypes and across iron-replete and low iron diets.
2018-12-12 | E-MTAB-7329 | biostudies-arrayexpress
Project description:Hepcidin is demonstrated to be the key iron regulatory hormone, produced by the liver. Here we show an unexpected role of hepcidin as a master initiator of the local and systemic inflammatory response. We demonstrated that Hepcidin is a key new essential component of the immune system and may be a promising target in many inflammatory diseases.
2021-02-13 | GSE95162 | GEO
Project description:Hepcidin is demonstrated to be the key iron regulatory hormone, produced by the liver. Here we show an unexpected role of hepcidin as a master initiator of the local and systemic inflammatory response. We found that hepcidin was highly expressed in the colon of two major idiopathic inflammatory bowel diseases : Crohn's disease (CD) and ulcerative colitis (UC). Thanks to the generation of intestinal specific hepcidin KO mice (Hepc{delta}int), we found in a DSS-induced colitis model that hepcidin mediated the induction of key inflammatory cytokines and was protective against intestinal injury. In a model of LPS-induced acute inflammation, intestinal hepcidin expression was increased through a TLR4 dependent pathway andwas required for intestinal neutrophil infiltration and inflammation. Strikingly, intestinal hepcidin was absolutely required for the systemic production of key inflammatory cytokines (IL-6, CXCL1, TNF-alpha ...) as well as for the setting of the hypoferremia of inflammation. In a sepsis model, Hepc{delta}int mice were protected against LPS-induced mortality. Mechanistically, we showed that hepcidin was a direct neutrophil chemoattractant and a proinflammatory molecule in macrophages through a Myd88 dependent pathway. Altogether, we demonstrated that Hepcidin is a key new essential component of the immune system and may be a promising target in many inflammatory diseases.
2019-02-14 | GSE71073 | GEO
Project description:Hepcidin is demonstrated to be the key iron regulatory hormone, produced by the liver. Here we show an unexpected role of hepcidin as a master initiator of the local and systemic inflammatory response. We found that hepcidin was highly expressed in the colon of two major idiopathic inflammatory bowel diseases : Crohn's disease (CD) and ulcerative colitis (UC). Thanks to the generation of intestinal specific hepcidin KO mice (Hepc{delta}int), we found in a DSS-induced colitis model that hepcidin mediated the induction of key inflammatory cytokines and was protective against intestinal injury. In a model of LPS-induced acute inflammation, intestinal hepcidin expression was increased through a TLR4 dependent pathway andwas required for intestinal neutrophil infiltration and inflammation. Strikingly, intestinal hepcidin was absolutely required for the systemic production of key inflammatory cytokines (IL-6, CXCL1, TNF-alpha ...) as well as for the setting of the hypoferremia of inflammation. In a sepsis model, Hepc{delta}int mice were protected against LPS-induced mortality. Mechanistically, we showed that hepcidin was a direct neutrophil chemoattractant and a proinflammatory molecule in macrophages through a Myd88 dependent pathway. Altogether, we demonstrated that Hepcidin is a key new essential component of the immune system and may be a promising target in many inflammatory diseases. We used microarrays to detail the global program of gene expression of BMDM treat with hepcidin for 1 hour.
2016-07-16 | E-GEOD-71073 | biostudies-arrayexpress
Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Global survey of gene expression in CAD cells and differentiated CAD neurons following lentiviral knockdown of ACSS2 or ATP citrate lyase (ACL) (and control = scramble hairpin); survey of hippocampal gene expression changes associated with retrieval of fear memory, after ACSS2-AAV knockdown or in EGFP-AAV control (comparison of 0h vs. 1h post-memory retrieval).
2017-05-01 | E-GEOD-76853 | biostudies-arrayexpress
Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and directchum regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Genome-wide examination of histone H3 and H4 acetylation, as well as ACSS2 binding, in undifferentiated CAD cells and differentiated CAD neurons; background adjusted by H3 ChIP or Input.
2017-05-01 | E-GEOD-76850 | biostudies-arrayexpress