Mechanistic Study on the Restoration of Intestinal Barrier Integrity and Alleviation of Inflammatory Bowel Disease by Rhynchophylline via the AhR-NR4A1 Pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1315156 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Restoring intestinal barrier function is considered an effective strategy for the treatment of Inflammatory Bowel Disease (IBD). Rhynchophylline (Rhy), a bioactive alkaloid sourced from the traditional herbs Uncariarhynchophylla used in Chinese medicine, is known for its antihypertensive, anti-asthmatic, and antitumor properties. This study explores the pharmacological effects and molecular mechanisms of Rhy in treating IBD.
2025-09-05 | GSE307290 | GEO
Project description:The AhR is a ligand activated transcription factor that may be important in normal skin physiology. We compared gene expression profiles between AhR Wt and AhR KO primary mouse keratinocyte cultures. We identified 391 genes that were differentially expressed with a 1.5 fold cutoff and p<.05, and identified the AhR as an important regulator of genes involved in normal epidermal differentiation. AhR Wt primary keratinocyte cultures (n=4) were compared with AhR KO primary keratinocyte cultures (n=3)
2015-07-01 | E-GEOD-62490 | biostudies-arrayexpress
Project description:Nr4a1 deficient rats (Nr4a1-/-) were developed using the fawn hooded hypertensive rat (FHH), which provided a genetic background susceptible to kidney injury. Both groups of animals were evaluated for blood pressure, proteinuria, renal function, and whole transcriptome gene pathway changes. Gene expression profiling was performed at week 8, 16, and 24 using kidney from FHH and Nr4a1-/- rats. To identify differentially expressed gene between FHH and Nr4a1-/- two statistical methods were utilized: (1) FWER (family-wise error rate) procedure, p<0.05 and fold-change M-BM-11.2 or greater; and/or (2) Benjamani and Hochberg FDR (false discovery rate) using p<0.05, and fold-change M-BM-11.2 or greater. Two-way ANOVA using a p<0.01 or lower was performed to identify strain X time interaction effects between groups. Gene networks and functional analysis were evaluated through the use of Ingenuity Pathways Analysis . FHH and Nr4a1-/- rats were grown to 8, 16, and 24 weeks of age and kidney tissue was harvested for transcriptome analysis (n=3 replicates/ per group/ time)
2014-02-06 | E-GEOD-54714 | biostudies-arrayexpress
Project description:The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants, however the precise molecular mechanisms remain unknown. The Aryl Hydrocarbon Receptor (AHR) is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression. Here, we show that ectopic activation of AHR during early differentiation disrupts the differentiation program via the chromatin remodeling complex NuRD. The activated AHR/NuRD complex altered the expression of differentiation-specific genes that control the first two developmental decisions without affecting the pluripotency program. These findings identify a novel mechanism that allows environmental stimuli to disrupt embryonic development through AHR signaling.
2018-02-26 | PXD006089 | Pride
Project description:The expression of NR4A1 was significantly reduced in radioresistant cells, namely MKN45-R and AGS-R, as opposed to their parental counterparts. Overexpressing NR4A1 in MKN45-R and AGS-R cells resulted in heightened sensitivity to radiation. Additionally, NR4A1 overexpression exerted inhibitory effects on the growth and metastasis of GC tissues in animal models following irradiation (IR). Our observations indicate that NR4A1 plays a crucial role in enhancing the radiation sensitivity of gastric cancer cells, underscoring the therapeutic potential of NR4A1 in GC treatment.
2025-05-24 | GSE286081 | GEO
Project description:The Aryl Hydrocarbon Receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanistically achieved remains poorly understood. We show that Hexokinase 2 (HK2) a metabolic enzyme fuelling cancer cell growth, is a transcriptional target of AHR as well as a modulator of its activity. Expression of HK2 is positively regulated by AHR upon exposure to agonists both in human cells and in mice lung tissues. Conversely, over-expression of HK2 regulates the abundance of many proteins involved in the regulation of AHR signalling and these changes are linked with altered AHR expression levels and transcriptional activity. HK2 expression also shows a negative correlation with AHR promoter methylation in tumours, and these tumours with high HK2 expression and low AHR methylation are associated with a worse overall survival in patients. In sum, our study provides novel insights into how AHR signalling is regulated which may help our understanding of the context-specific effects of this pathway and may have implications in cancer.
2022-05-31 | PXD028992 | Pride
Project description:We investigate the cellular and molecular mechanisms of tumor suppression by NR4A1 and NR4A3, and show a cell intrinsic essential function in maintenance of hematopoietic stem cell (HSC) homeostasis. In the absence of Nr4a1/3, HSC lost quiescence, became highly proliferative leukemia-stem cell (LSC) that transplanted AML to recipient mice. We further revealed that loss of NR4A1/3 leads to deregulated expression of the key cell cycle regulator Cdkn1c (P57), c-Myc oncogene, and glucose metabolic genes leading to enhanced aerobic glycolysis or Warburg effect in LSCs. Reintroduction of Nr4a1 in LSCs restored HSC quiescence, and reversed Nr4a1/3 deficiency induced P57 suppression and c-Myc overexpression. Collectively, we identify an essential role of Nr4a1/3 in coordinately regulating cell cycle entry and glucose metabolism to prevent uncontrolled stem cell proliferation and AML transformation. These results have major implications for designing therapeutic strategies in AML. To identify NR4A-dependent molecular signaling pathways that may control HSC homeostasis, we performed genome-wide transcript profiling of Lin-Sca1+ (LS) cells from WT and DKO mice. For Affymetrix analysis, we generated three independent pools of RNA from sorted LS cells from 10-20 WT or DKO (2- to 3-week-old) mice per sample.
2013-12-30 | E-GEOD-31042 | biostudies-arrayexpress
Project description:Excitatory synapses occur mainly on dendritic spines, and spine density is usually correlated with the strength of excitatory synaptic transmission. We report that Nr4a1, an activity-inducible gene encoding a nuclear receptor, regulates the density and distribution of dendritic spines in CA1 pyramidal neurons. Nr4a1 overexpression resulted in elimination of the majority of spines; however, postsynaptic densities were preserved on dendritic shafts, and the strength of excitatory synaptic transmission was unaffected, showing that excitatory synapses can be dissociated from spines. mRNA expression profiling studies suggest that Nr4a1-mediated transcriptional regulation of the actin cytoskeleton contributes to this effect. Under conditions of chronically elevated activity, when Nr4a1 was induced, Nr4a1 knockdown increased the density of spines and PSDs specifically at the distal ends of dendrites. Thus, Nr4a1 is a key component of an activity-induced transcriptional program that regulates the density and distribution of spines and synapses. After 10 days in culture, dissociated mouse hippocampal neurons in 6-well plates were infected with lentivirus expressing either Flag-Nr4a1 or GFP and incubated for 6 days to allow for transgene expression. Total RNA was then isolated using RNeasy Plus kit (QIAGEN). Samples passing an mRNA quality check proceeded to quantitative analysis on Agilent-026655 4x44 Mouse Microarrays.
2016-01-13 | E-GEOD-76805 | biostudies-arrayexpress
Project description:Investigation of differentially expressed genes in circZbtb20 or Nr4a1 deficient ILC3s
2020-04-20 | GSE148456 | GEO