Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Urolithin A is a potent modulator of cGAS-Sting signaling pathway

ABSTRACT: The innate immune cGAS-STING pathway has emerged as an important signaling system in the organismal defense against viral and bacterial infections, inflammatory responses to cellular damage, regulation of autophagy, as well as in tumor immunosurveillance. Such key functions of the cGAS-STING pathway make it an attractive target for pharmacological intervention in disease treatments and in controlling inflammation and immunity. Here, we show that urolithin A (UA), an ellagic acid metabolite, exerts a profound effect on the expression of STING and enhances cGAS-STING activation and STING-related autophagy in response to cytosolic DNA in human cell lines. Animal laboratory models and limited human trials have reported no obvious adverse effects of UA administration. Thus, the use of UA alone or in combination with other pharmacological compounds may present a potential therapeutic approach in the treatment of human diseases that involves aberrant activation of the cGAS-STING pathway or accumulation of cytosolic DNA and warrants further investigation in relevant transgenic animal models.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224258 | GEO | 2025/09/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Long-term Urolithin A treatment ameliorates disease pathology in Alzheimer's Disease mouse models [MET_DC]

Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with learning, memory, and cognitive deficits. Neuroinflammation and lysosomal dysfunction are thought to play key roles in the progression of AD pathology. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Urolithin A (UA) is a gut microbial metabolite of ellagic acid shown to stimulate mitophagy and acts as a potent anti-inflammatory and anti-oxidant agent. However, long-term safety and the potential role of UA in altering pathology of AD is still largely unclear. In this study, we investigated the underlying mechanisms for the beneficial effects of UA in multiple mouse models of AD. We report that long-term UA treatment significantly improves learning and memory, olfactory function, and synaptic function of neurons in AD transgenic mice. We demonstrate that UA decreases soluble and insoluble Ab1-42, total Tau, and Tau phosphorylation. Furthermore, alterations in lysosomal cathepsins, particularly upregulation of cathepsin Z, was observed in the AD mice brains and normalized by UA treatment. Notably, UA treatment also ameliorates neuroinflammation, DNA damage, mitochondrial dysfunction, and restores lysosomal functions in AD mice brains. Collectively, these results provide new insights into the role of UA in regulating lysosomal dysfunction, cathepsins, and suggests that UA may have a potential therapeutic application for AD. To understand what metabolism-related gene expression changes are induced by Urolithin A, WT (C57BL6/J), 3xTgAD and 3xTgAD/PolB+/- mice were treated with water or Urolithin A (200mg/kg/day) by oral gavage for 5 months starting when the mice were 12m of age, thereafter hippocampi tissues was collected from each mouse and subjected to RNA isolation.

2024-07-01 | GSE214416 | GEO

Long-term Urolithin A treatment ameliorates disease pathology in Alzheimer's Disease mouse models [AD_DC]

Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with learning, memory, and cognitive deficits. Neuroinflammation and lysosomal dysfunction are thought to play key roles in the progression of AD pathology. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Urolithin A (UA) is a gut microbial metabolite of ellagic acid shown to stimulate mitophagy and acts as a potent anti-inflammatory and anti-oxidant agent. However, long-term safety and the potential role of UA in altering pathology of AD is still largely unclear. In this study, we investigated the underlying mechanisms for the beneficial effects of UA in multiple mouse models of AD. We report that long-term UA treatment significantly improves learning and memory, olfactory function, and synaptic function of neurons in AD transgenic mice. We demonstrate that UA decreases soluble and insoluble Ab1-42, total Tau, and Tau phosphorylation. Furthermore, alterations in lysosomal cathepsins, particularly upregulation of cathepsin Z, was observed in the AD mice brains and normalized by UA treatment. Notably, UA treatment also ameliorates neuroinflammation, DNA damage, mitochondrial dysfunction, and restores lysosomal functions in AD mice brains. Collectively, these results provide new insights into the role of UA in regulating lysosomal dysfunction, cathepsins, and suggests that UA may have a potential therapeutic application for AD. To understand what gene expression changes are induced by Urolithin A, WT (C57BL6/J), 3xTgAD and 3xTgAD/PolB+/- mice were treated with water or Urolithin A (200mg/kg/day) by oral gavage for 5 months starting when the mice were 12m of age. Thereafter, hippocampi tissue was collected from each mouse and subjected to RNA isolation.

2024-07-01 | GSE214406 | GEO

Long-term Urolithin A treatment ameliorates disease pathology in Alzheimer's Disease mouse models [I]

2024-07-01 | GSE212972 | GEO

Urolithin A is a potent modulator of cGAS-Sting signaling pathway

Project description:Urolithin A is a potent modulator of cGAS-Sting signaling pathway

| PRJNA930416 | ENA

Gene expression after 24h Urolithin A incubation in LNCaP cells

Project description:The identification of new agents that may modulate the progression of cancer cell growth is of great interest. In this regard, dietary agents can be utilized to identify molecular targets to be used as part of a chemopreventive strategy. Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). We performed a genomic analysis to study the effect of UA on androgen-dependent LNCaP prostate adenocarcinoma cells. Cells were incubated with 40ÂµM UA for 24 hours, then, RNA was extracted. RNA samples were processed in the automated Biomek FX System (Beckman Coulter), where aRNA was produced, and labeled with Biotin, purified , fragmented and hybridized onto HG U219-24 Array, using the GeneChip HT 3âIVT Express Kit . Afterwards, the GeneTitanÂ® Multi-Channel (MC) Instrument (Affymetrix) was used to hybridize, wash , stain , and scan the arrays. Microarray results were analyzed using the GeneSpring GX v13.0 software. LNCaP cells were plated in 35mm wells, the following day they were treated with 40ÂµM urolithin A (UA) for 24 hours, after incubation Total RNA was extracted using Qiagen RNAeasy minikit. The Affymetrix Human Genome U219 array plate was used, which measures gene expression of more than 36 000 transcripts and variants per sample, which represent more than 20 000 genes.

2016-07-27 | E-GEOD-65527 | biostudies-arrayexpress

Neuroretina of young and old mice treated with UA or vehicle

Project description:Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy was either increased or unchanged in old versus young mice. Transcriptomic analysis showed marked upregulation of the type I interferon response in the retina of old mice, an effect that correlated with increased levels of cytosolic mtDNA and activation of the cGAS/STING pathway. Crucially, these same alterations were replicated in primary human fibroblasts from elderly donors. In old mice, pharmacological induction of mitophagy with urolithin A attenuated cGAS/STING activation and ameliorated deterioration of neurological function. These findings point to induction of mitophagy as a novel strategy to decrease age-associated inflammation and increase healthspan.

2023-12-18 | GSE231882 | GEO

CT26 sorted in vivo tumor cells with Trex1 KO

Project description:The DNA exonuclease TREX1 degrades endogenous cytosolic DNA. Cytosolic DNA triggers the cGAS/STING pathway which increases type I interferon. To investigate the physiological significance of TREX1 loss on in vivo tumor growth, we implanted control and TREX1-deficient CT26 tumor cells into immunocompetent BALB/c hosts.Tumor cells were collected 7 days after tumors reached around 200mm3.

2024-03-12 | E-MTAB-13816 | biostudies-arrayexpress

Urolithin A and Nicotinamide Riboside differentially regulate innate immune defenses and metabolism.

Project description:During aging, general cellular processes such as autophagic clearance, DNA repair, mitochondrial health, metabolism, nicotinamide adenine dinucleotide (NAD+) levels, and immunological responses become compromised. Urolithin A (UA) and NAD+ supplementation stimulate mitophagy, reduce pathological plaque load, and inflammation while improving learning in models of Alzheimer’s disease (Hou et al 2021; Fang et al 2019). Here we have performed a During aging, general cellular processes such as autophagic clearance, DNA repair, mitochondrial health, metabolism, nicotinamide adenine dinucleotide (NAD+) levels, and immunological responses become compromised. Urolithin A (UA) and NAD+ supplementation stimulate mitophagy, reduce pathological plaque load, and inflammation while improving learning in models of Alzheimer’s disease (Hou et al 2021; Fang et al 2019). Here we have performed a pairwise analysis of UA and nicotinamide riboside (NR) to investigate how these compounds modulate inflammation. The role of microglia in driving neuroinflammation is becoming more recognized in several neurodegenerative diseases, yet the effects of these drugs on microglia cells have not been thoroughly investigated. As both UA and NR are recognized as safe dietary supplements, their function in normal cells is equally important to understand as in a disease state. Here we investigated the effects of UA and NR in the human microglia cell line, HMC3.

2024-12-19 | GSE266162 | GEO

Urolithin A mitigates behavioral and synaptic deficits associated with epilepsy through VDAC-1 inhibition: A novel treatment approach

Project description:Supplementation of Urolithin-A, a catabolite of ellagic acid-containing precursors, has been shown to benefit the central nervous system (CNS). This study focused on deciphering the potential anti-epileptic effects of Urolithin-A, a small molecule of natural origin. To understand the primary underlying mediators of UA’s anti-epileptic efficacy, RNA sequencing was performed in the sub-acute epileptic model of Drosophila (4 hours of treatment duration with epileptic inducer-picrotoxin (PTX)) to abstain from the interference of secondary pathways. Four treatment groups were included in the study: 1) Vehicle (0.5% DMSO), 2) 1mM PTX, 3) 1mM PTX + Urolithin-A (100µM), and 4) Urolithin-A (100µM). Administration of Urolithin-A restores the PTX-induced misregulated genes of brain hemolymph and metabolic dysfunctions.

2025-04-09 | GSE263560 | GEO

Gene expression after 24h Urolithin A incubation in LNCaP cells

Project description:The identification of new agents that may modulate the progression of cancer cell growth is of great interest. In this regard, dietary agents can be utilized to identify molecular targets to be used as part of a chemopreventive strategy. Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). We performed a genomic analysis to study the effect of UA on androgen-dependent LNCaP prostate adenocarcinoma cells. Cells were incubated with 40µM UA for 24 hours, then, RNA was extracted. RNA samples were processed in the automated Biomek FX System (Beckman Coulter), where aRNA was produced, and labeled with Biotin, purified , fragmented and hybridized onto HG U219-24 Array, using the GeneChip HT 3’IVT Express Kit . Afterwards, the GeneTitan® Multi-Channel (MC) Instrument (Affymetrix) was used to hybridize, wash , stain , and scan the arrays. Microarray results were analyzed using the GeneSpring GX v13.0 software.

2016-07-27 | GSE65527 | 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