Epigallocatechin gallate delays age-related cataract development via the RASSF2/AKT pathway
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE212348 | GEO | 2023/08/23
REPOSITORIES: GEO
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Project description:Epigallocatechin gallate delays age-related cataract development via the RASSF2/AKT pathway
| PRJNA875091 | ENA
Project description:We have identified Epigallocatechin Gallate (EGCG) as a potent modulator of microglia function. Our aim was to determine whether EGCG affects the transcriptome of microglia and identify genes and gene sets that may underly the effects of EGCG on microglia function.
2024-07-17 | GSE208144 | GEO
Project description:Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to downregulate inflammatory responses in macrophages; however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor that mediates the anti-cancer action of EGCG at physiologically relevant concentrations (0.1-1 mM). Here we show the molecular basis for the downregulation of TLR4 signal transduction by EGCG at 1 mM in macrophages. Anti-67LR antibody treatment or RNAi-mediated silencing of 67LR resulted in abrogation of the inhibitory action of EGCG on LPS-induced activation of downstream signaling pathways and target gene expressions. Additionally, we found that EGCG reduced the TLR4 expression through 67LR. Interestingly, EGCG induced a rapid upregulation of Tollip protein, a negative regulator of TLR-signaling, and this EGCG action was prevented by 67LR silencing or anti-67LR antibody treatment. RNAi-mediated silencing of Tollip impaired the TLR4 signaling inhibitory activity of EGCG. Taken together, these findings demonstrate that 67LR plays a critical role in mediating anti-inflammatory action of a physiologically relevant EGCG and Tollip expression could be modulated through 67LR. These results provide a new insight into the understanding of negative regulatory mechanisms for TLR4 signaling pathway and consequent inflammatory responses which are implicated in the development and progression of many chronic diseases. We quantified expression profile of 210 inflammatory-relating genes in the 67LR-downregulated cells treated with LPS or/and EGCG by microarray
2010-04-20 | E-GEOD-21320 | biostudies-arrayexpress
Project description:Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to downregulate inflammatory responses in macrophages; however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor that mediates the anti-cancer action of EGCG at physiologically relevant concentrations (0.1-1 mM). Here we show the molecular basis for the downregulation of TLR4 signal transduction by EGCG at 1 mM in macrophages. Anti-67LR antibody treatment or RNAi-mediated silencing of 67LR resulted in abrogation of the inhibitory action of EGCG on LPS-induced activation of downstream signaling pathways and target gene expressions. Additionally, we found that EGCG reduced the TLR4 expression through 67LR. Interestingly, EGCG induced a rapid upregulation of Tollip protein, a negative regulator of TLR-signaling, and this EGCG action was prevented by 67LR silencing or anti-67LR antibody treatment. RNAi-mediated silencing of Tollip impaired the TLR4 signaling inhibitory activity of EGCG. Taken together, these findings demonstrate that 67LR plays a critical role in mediating anti-inflammatory action of a physiologically relevant EGCG and Tollip expression could be modulated through 67LR. These results provide a new insight into the understanding of negative regulatory mechanisms for TLR4 signaling pathway and consequent inflammatory responses which are implicated in the development and progression of many chronic diseases.
2010-04-20 | GSE21320 | GEO
Project description:The inhibition of DYRK1A (Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase 1A) activity, triplicated in trisomy 21 subjects, has been proved as a promising therapy for Down syndrome. Epigallocatechin-3-gallate (EGCG), a polyphenol of green tea, is an allosteric inhibitor of DYRK1A that showed beneficial pro-cognitive effects in clinical trials with DS individuals. However, EGCG induces several pharmacological effects, and there is no proof that the observed improvements result from DYRK1A inhibition. Besides, the direct consequences of Dyrk1A overexpression are not well defined. We therefore used quantitative proteomics to decipher the proteome and phosphoproteome alterations resulting from Dyrk1A overexpression and its inhibition to get insight into the mechanism of action of EGCG. Towards this aim, we used mice overexpressing Dyrk1A, and compared the hippocampal proteome and phosphoproteome with their wild type counterparts, in basal conditions, and after treatment with EGCG. Moreover, given that the human clinical trials found that the effects of EGCG potentiated the effects of cognitive stimulation, we also included in our study treatment with environmental enrichment and its combination with EGCG. We found that DYRK1A overexpression leads to alterations in protein and phosphoprotein levels of hundreds of proteins, and that the levels of proteins involved in key postsynaptic pathways are restored by the cognitive enhancer treatments, which could help conceiving new therapeutic strategies.
2019-12-11 | PXD010689 | Pride
Project description:Alzheimer’s disease (AD) is the most common form of adult-onset dementia with severe intellectual deterioration and is characterised by the accumulation of the amyloid-β (Aβ) peptides and the presence of hyperphosphorylated microtubule- associated protein, tau. (-)-Epigallocatechin-3-gallate (EGCG) – a polyphenolic catechin found in green tea leaves, not only acts as a proteasome inhibitor, it is also involved in neuroprotection. A total of 7 RNA samples were analyzed. Cultured murine primary cortical neurons were treated with 1uM EGCG for 24h (n=3) in addition to the vehicle control (n=4).
2013-12-31 | E-GEOD-22996 | biostudies-arrayexpress
Project description:As an ageing population trend, age-related cataracts (ARC) continue to be the primary cause of reversible severe vision impairment and blindness worldwide, with an increasing incidence. The primary disease mechanism of ARC formation is metabolic abnormalities and oxidative stress mainly caused by increasing age. Additionally, ultraviolet B exposure, systematic disease factors (diabetes and hypertension), and lifestyle factors (smoking, drinking, and malnutrition) are the risk factors for ARC formation. Although surgical removal of the onset lens and replacement of the intraocular lens is currently the only effective treatment method with a high success rate and a high-cost fee, cataracts have so far lacked effective therapeutic drugs leading to a heavy burden on the patient's family and society. Therefore, we performed transcriptomic analysis of human lens and ARC to investigate the possible pathogenesis of lens opacification in ageing people.
2023-02-23 | GSE213546 | GEO
Project description:We reported the molecular mechanisms of low combination doses of epigallocatechin-3-gallate and hydroxychavicol (EGCG+HC) in glioma cell lines 1321N1 and LN18. Using high throughput RNA sequencing, combined EGCG+HC exerted its anticancer effect by downregulating the axon guidance process and metabolic pathways, while simultaneously interfering with endoplasmic reticulum unfolded protein response pathway. Furthermore, EGCG+HC exerted its apoptotic effect through the alteration of mitochondrial genes such as MT-CO3 and MT-RNR2 in 1321N1 and LN18 cells respectively. EGCG+HC dynamically altered DYNLL1 alternative splicing expression in 1321N1 and DLD splicing expression in LN18 cell lines.
2022-04-13 | GSE193838 | GEO
Project description:Background: Hepatocellular carcinoma (HCC) is increasing in incidence and treatment is often unsuccessful. Thus, prevention in high-risk patients with established cirrhosis has been proposed as an alternative strategy. It has been suggested that the increased inflammation and fibrogenesis observed during cirrhosis predisposes the liver to future malignant transformation to HCC through a “field effect”. A growing body of evidence indicates that the green tea polyphenol, (-)-epigallocatechin gallate (EGCG), can reduce inflammation and fibrogenesis during chronic liver injury. Here, we test the hypothesis that EGCG administered in the setting of cirrhosis can prevent future HCC development. Methods: A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the efficacy of EGCG for inhibition of HCC formation in these cirrhotic livers. DEN (50 mg/kg) was administered weekly throughout the study while 0.02% EGCG was given in drinking water beginning at the onset of cirrhosis. At the end of the study, rats were sacrificed, livers were sectioned and stained to analyze disease progression and tumor nodules were counted. Liver function tests were performed to determine liver injury and overall liver function. Finally, genome-wide gene expression profiling on the surrounding, non-tumoral liver tissue was used to monitor the “field effect” in response to EGCG. Results: EGCG significantly (p < 0.01) prevented the development of HCC tumor nodules from on average 18.8 in vehicle controls to on average 9.1 in EGCG-treated animals. EGCG also reduced liver injury and improved liver function as assessed by serum chemistry tests. Finally, a gene expression signature predictive of poor survival and HCC development in human cirrhosis patients was reversed in response to EGCG. Conclusions: Our data are consistent with the growing body of evidence suggesting that EGCG has protective effects in liver disease. Further, our results suggest that EGCG is a potentially effective HCC prevention strategy that can be monitored using gene expression signatures.
2020-03-10 | GSE67880 | GEO
Project description:Epigallocatechin gallate (EGCG), the major green tea polyphenol, has been a subject of global interest as a potential chemopreventive or chemotherapeutic supplement for breast cancer. While on one hand epidemiological studies suggest inverse correlation between green tea consumption and breast cancer risk, investigations using cell culture and animal models of breast carcinogenesis on the other hand have demonstrated antiproliferative, antitumor, anti-invasive and anti-metastatic properties of EGCG. Mechanism of how EGCG affects cell proliferation, apoptosis, migration and cell cycle by affecting the function of a wide range of molecular targets have also been studied. However, the question as to how EGCG impacts on estrogen responsive genes has not been addressed. This issue is of relevance to our notion of EGCG as a potential chemopreventive or chemotherapeutic agent against breast cancer, which is estrogen dependent in majority of the newly diagnosed cases. Here, using the estrogen receptor α (ERα) positive MCF-7 breast cancer cells as a model, we have examined the effect of EGCG on the estrogen regulated genes. MCF7 cells were treated with vehicle (Ethanol) or EGCG in the presence or absence of estrogen for 24hrs. Total RNA was extracted; Cy3 labeled cRNA was hybridized to Genotypic Technology designed Custom Human Whole Genome 8x60k Microarray (Agilent-027114). Median signal intensities were used for the analysis. After background subtraction (normexp) and normalization (quantile) differentially expressed genes were identified using linear models.
2015-04-01 | E-GEOD-56245 | biostudies-arrayexpress