Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inflammation Impacts Androgen Receptor Signaling in Basal Prostate Stem Cells Through Interleukin 1 Receptor Antagonist

ABSTRACT: Chronic prostate inflammation in patients with benign prostate hyperplasia (BPH) correlates with the severity of symptoms. How inflammation contributes to prostate enlargement and/or BPH symptoms and the underlying mechanisms remain unclear. In this study, we utilized a unique transgenic mouse model that mimics chronic non-bacterial prostatitis in men and investigated the impact of inflammation on androgen receptor (AR) in basal prostate stem cells (bPSC) and their differentiation in vivo. We found that inflammation significantly enhanced AR levels and activity in bPSC. More importantly, we identified interleukin 1 receptor antagonist (IL-1RA) as a crucial regulator of AR in bPSC during inflammation. IL-1RA was one of the top genes upregulated by inflammation, and inhibiting IL-1RA reversed the enhanced AR activity in organoids derived from inflamed bPSC. Additionally, IL-1RA appeared to activate AR by counteracting IL-1's inhibitory effect. Furthermore, using a lineage tracing model, we observed that inflammation induced bPSC proliferation and differentiation into luminal cells even under castrate conditions, indicating that AR activation driven by inflammation is sufficient to promote bPSC proliferation and differentiation. Taken together, our study uncovered novel mechanisms through which inflammation modulates AR signaling in bPSC and induces bPSC luminal differentiation that may contribute to prostate hyperplasia.

ORGANISM(S): Mus musculus

PROVIDER: GSE269582 | GEO | 2024/06/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Inflammation Impacts Androgen Receptor Signaling in Basal Prostate Stem Cells Through Interleukin 1 Receptor Antagonist [Cut & Tag]

Project description:Chronic prostate inflammation in patients with benign prostate hyperplasia (BPH) correlates with the severity of symptoms. How inflammation contributes to prostate enlargement and/or BPH symptoms and the underlying mechanisms remain unclear. In this study, we utilized a unique transgenic mouse model that mimicschronicnon-bacterial prostatitis in men and investigated the impact of inflammation on androgen receptor (AR) in basal prostate stem cells (bPSC) and their differentiationin vivo. We found that inflammation significantly enhanced AR levels and activity in bPSC. More importantly, we identified interleukin 1 receptor antagonist (IL-1RA) as a crucial regulator of AR in bPSC during inflammation. IL-1RA was one of the top genes upregulated by inflammation, and inhibiting IL-1RA reversed the enhanced AR activity in organoids derived from inflamed bPSC. Additionally, IL-1RA appeared to activate AR by counteracting IL-1a's inhibitory effect. Furthermore, using a lineage tracing model, we observed that inflammation induced bPSC proliferation and differentiation into luminal cells even under castrate conditions, indicating that AR activation driven by inflammation is sufficient to promote bPSC proliferation and differentiation. Taken together, our study uncovered novel mechanisms through which inflammation modulates AR signaling in bPSC and induces bPSC luminal differentiation that may contribute to prostate hyperplasia.

2024-06-26 | GSE269548 | GEO

Gene expression profiling of AR deletion in prostate luminal cells

Project description:Benign prostatic hyperplasia (BPH) is a common urological disease that adversely affects quality of life among elderly males, but its etiology remains poorly understood. We show that the expression of the androgen receptor (AR) is decreased in the luminal epithelial cells of human BPH specimens and is inversely correlated with the degree of regional prostatic inflammation.

2016-09-27 | GSE77646 | GEO

ESR1+ luminal epithelial cells contribute to androgen-independent prostate survival in the absence of SRD5A2

Project description:Steroid 5α reductase 2 (SRD5A2) is crucial for prostatic development, converting testosterone to dihydrotestosterone (DHT). While 5α reductase inhibitors (5ARI) effectively reduce prostate size in benign prostate hyperplasia (BPH), their limited efficacy against BPH-related lower urinary tract symptoms (LUTS) and mechanisms of 5ARI resistance remain unclear. Here, we developed a Srd5a2-/- mouse model and employed single-cell RNA sequencing (scRNA-seq) to explore the impact of SRD5A2 absence on prostate cellular heterogeneity. Significant alterations in luminal epithelial (LE) populations were observed, alongside increased proportion and proliferative phenotype of estrogen receptor 1 (ESR1)+ Luminal Epithelia 2 (LE2) cells, following an SRD5A2-independent ESR1 differentiation trajectory. LE2 cells exhibited enhanced estrogen response gene signatures, suggesting alternative pathways for prostate growth without SRD5A2. Human prostate biopsy analysis revealed an inverse correlation between SRD5A2 expression and LE2 markers (ESR1 and PKCα). These findings provide insights into prostate biology, 5ARI resistance mechanisms, and potential targeted therapies for BPH-related LUTS.

2023-06-26 | GSE235514 | GEO

Prostates of rats with induced partial bladder outlet obstruction and the effect of Eviprostat on those changes

Project description:Prostatic inflammation plays a role in the progression of benign prostatic hyperplasia (BPH). Eviprostat is an antiinflammatory and antioxidant phytotherapeutic agent widely used to treat lower urinary tract symptoms in BPH. However, because Eviprostat is a mixture of compounds from multiple natural sources, its mechanism of action has been difficult to investigate. In this study, we used oligonucleotide microarrays to identify changes in gene expression that occur in the prostate of rats with surgically induced partial bladder outlet obstruction and the effect of Eviprostat on those changes.

2009-07-21 | GSE16063 | GEO

Opposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor Î² (ERÎ²) Response to 5Î±-reductase Inhibition in Prostate Epithelial Cells

Project description:Current pharmacotherapies for symptomatic benign prostatic hyperplasia (BPH), an androgen receptor (AR) driven, inflammatory disorder affecting elderly men, include 5Î±-reductase (5AR) inhibitors (i.e. dutasteride and finasteride) to block the conversion of testosterone to the more potent AR ligand dihydrotestosterone (DHT). Since DHT is the precursor for estrogen receptor Î² (ERÎ²) ligands, 5AR inhibitors could potentially limit ERÎ² activation, which maintains prostate tissue homeostasis. We have uncovered signaling pathways in BPH-derived prostate epithelial cells (BPH-1) that are impacted by 5AR inhibition. The induction of apoptosis and repression of the cell-adhesion protein E-cadherin by the 5AR inhibitor, dutasteride, requires both ERÎ² and TGFÎ². Dutasteride also induces cyclooxygenase type 2 (COX-2), which functions in a negative-feedback loop in TGFÎ² and ERÎ² signaling pathways as evidenced by the potentiation of apoptosis induced by dutasteride or finasteride upon pharmacological inhibition or shRNA-mediated ablation of COX-2. Concurrently, COX-2 positively impacts ERÎ² action through its effect on the expression of a number of steroidogenic enzymes in the ERÎ²-ligand metabolic pathway. Therefore, effective combination pharmacotherapies, which have included non-steroidal anti-inflammatory drugs, must take into account biochemical pathways affected by 5AR inhibition and opposing effects of COX-2 on the tissue protective action of ERÎ². Next-generation sequencing (n=3) of shRNA mediated knockdown of COX-2 or scrambled control in BPH-1 prostate epithelial cell line

2016-05-12 | E-GEOD-80979 | biostudies-arrayexpress

Restricted regulation of gene expression in benign prostate epithelial cell models

Project description:Investigation if GATA-2 and NKX3-1 exogenous expression in prostate basal-like prostate epithelial cells could induce AR transcription and luminal differentiation

2021-02-21 | E-MTAB-8487 | biostudies-arrayexpress

Expression data from Incidental vs. Surgical BPH samples

Project description:used to identify differences between tissues from patients undergoing surgery for BPH with unresolved symptoms compared to incidental BPH from patients with prostate cancer

2015-01-27 | GSE65343 | GEO

Expression data from Incidental vs. Surgical BPH samples

Project description:used to identify differences between tissues from patients undergoing surgery for BPH with unresolved symptoms compared to incidental BPH from patients with prostate cancer cohorts are based on surgical distinction

2015-01-27 | E-GEOD-65343 | biostudies-arrayexpress

Therapeutic potential of pomegranate juice-derived nanovesicles in nude mouse benign prostatic hyperplasia (BPH) xenograft model

Project description:Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms affect a large percentage of the male population and places a substantial burden on the world health system. Current therapies include 5-alpha reductase inhibitors and alpha-blockers that are only partially effective and pose a huge economic burden, emphasizing the urgent need for effective, economical therapies. We isolated nanovesicles from pomegranate juice (Punica Granatum) (referred to as ‘POM-NVs’) and report to our knowledge for the first time, that these vesicles possess therapeutic potential against BPH. Following extensive characterization of POM-NVs, we tested their therapeutic potential in vitro using BPH1 cell line and identified a potential anti-proliferative and pro-apoptotic effect. We further tested these vesicles using a clinically relevant xenograft mouse BPH model derived from human BPH tissues. Remarkably, POM-NVs could reverse the BPH phenotype conferred by TGF-β mediated signaling and induced epithelial-to-mesenchymal (EMT) reversal, leading to the restoration of prostate epithelial states in vivo and in vitro. Furthermore, these vesicles attenuated bone morphogenic protein 5 (BMP5) signaling, a cardinal alteration that is instrumental in driving BPH. Considering the large incidences of BPH and its associated economic burdens, our study has important implications and can potentially improve the clinical management of BPH.

2023-07-18 | PXD043608 | Pride

Gene expression profiling of mouse prostate over-expressing the Notch1 intracellular domain.

Project description:Molecular signaling that regulates differentiation, survival and proliferation of the prostate luminal epithelial cells has not been thoroughly understood. Herein, we show that increased canonical Notch1 activity suppresses terminal differentiation of prostate luminal epithelial cells but is insufficient to transform. Augmented Notch1 activity delays anoikis of luminal epithelial cells by augmenting NF-κB activity independent of Hes-1, stimulates luminal cell proliferation by potentiating the PI3K-AKT signaling, and rescues the capacities of a fraction of prostate luminal epithelial cells for unipotent differentiation in vivo and short-term self-renewal in vitro. Epithelial cell-autonomous AR signaling is dispensable for the Notch-mediated cellular survival and proliferation. This study reveals a previously unappreciated role of Notch in prostatic luminal epithelial cell differentiation, supports the presence of a lineage hierarchy within the prostate luminal epithelial cells, and implies a pro-metastatic function of Notch signaling during prostate cancer progression. Two group comparison (WT and Mut)

2014-08-07 | E-GEOD-53036 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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