Host susceptibility to recurrent cystitis is shaped by bladder TNF-alpha signaling dynamics
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA482406 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7553980_1.fastq.gz | Fastqsanger.gz | |||
| SRR7553980_2.fastq.gz | Fastqsanger.gz | |||
| SRR7553990_1.fastq.gz | Fastqsanger.gz | |||
| SRR7553990_2.fastq.gz | Fastqsanger.gz | |||
| SRR7554000_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 293 |
Similar Datasets
Project description:Urinary tract infections (UTI) are common and recurrent. Both host genetics and UTI history impact susceptibility to recurrent UTI (rUTI) in women and in animal models. To identify shared patterns of host response that correlate with susceptibility, we investigated bladder inflammatory and transcriptional kinetics in acute and rUTI models. We found that TNFɑ signaling kinetics differed with mouse strain and infection history. Mice resistant to severe UTI/rUTI displayed a robust TNFɑ-dependent inflammation during the first 6 hours of acute cystitis, which waned by 24 hours; mice that are susceptible varied in their early responses but were prone to severe inflammation at 24 hours post-infection. Depletion of TNFɑ in an rUTI model revealed that early TNFɑ signaling promoted colonization resistance via exfoliation of infected bladder cells, but prolonged TNFɑ signaling exacerbated inflammation, thereby worsening infection. Host genetics and disease history impacts susceptibility by regulating the kinetics of a common TNFɑ pathway.
2019-07-21 | GSE117532 | GEO
Project description:Cystitis is a bacterial infection of the bladder that occurs in about half of women at least once in their lifetime. Antibiotics such as nitrofurantoin are used to treat cystitis but antibiotic resistance is a concern, especially for recurrent infections. Here we report an open label, randomized, single-center, phase 2 study to analyze the acute and long-term safety and efficacy of the IL-1 receptor antagonist anakinra, compared to nitrofurantoin, in recurrent cystitis. Thirty adult female patients with a documented history of recurrent cystitis and a current acute cystitis episode were randomized in a 2:1 ratio to treatment with anakinra (n=20) or nitrofurantoin (n=10) for five days. Primary and secondary efficacy end points were reached, defined as the reduction in typical symptoms, measured by the acute cystitis symptom score (ACSS, day 5), longitudinal symptom scores, recurrence rates, quality of life gene, expression analysis and microbiology at follow-up on days 15, 30 and at six months. Symptom scores were decreased in the anakinra (P<0.001), and nitrofurantoin (P<0.001) arms after five days and remained low after 15, 30 days and 6 months. Recurrences were less frequent after 6 months in both treatment groups compared to the 6-month pre-enrolment history (P<0.001 for anakinra and P=0.004 for nitrofurantoin) and the quality of life was increased, without adverse effects. Immune gene expression was rapidly inhibited in the anakinra treated patients but not in the nitrofurantoin group. Targeted innate immune inhibition therapy shows non-inferiority to nitrofurantoin in patients with recurrent acute cystitis (German Clinical Trials Register, DRKS00025964; EudraCT, 2019-004209-28).
2026-01-30 | GSE315861 | GEO
Project description:Interstitial cystitis (IC) and bladder pain syndrome are terms used to describe a heterogenous chronic pelvic and bladder pain disorder of unknown etiology. The goal of this pilot study was to determine if gene expression profiling of bladder biopsy tissue from patients experiencing symptoms could be used to separate the patients based on some clinical parameter.
2014-05-13 | GSE57560 | GEO
Project description:Targeted innate immune inhibition therapy compared to antibiotics for recurrent acute cystitis
| PRJNA1399454 | ENA
Project description:Mice were infected with the cystitis isolate UTI89 transurethrally and sacrificed 28 days post infection. Total bladder RNA was harvested from mock, resolved or chronic bladder and analyzed using the mouse gene 1.0 st chips.
2014-12-06 | E-MTAB-2930 | biostudies-arrayexpress
Project description:Interstitial cystitis (IC) and bladder pain syndrome are terms used to describe a heterogenous chronic pelvic and bladder pain disorder of unknown etiology. The goal of this pilot study was to determine if gene expression profiling of bladder biopsy tissue from patients experiencing symptoms could be used to separate the patients based on some clinical parameter. Gene expression profiles in bladder biopsy tissue from patients with: (1) low bladder capacity (defined here as <400 ml upon hydordistension), (2) normal capacity (M-bM-^IM-%400 ml), and (3) controls were compared. Gene expression profiles from low bladder capacity tissues differed significantly from normal capacity and control tissue, suggesting gene expression profiling may be a useful tool for better understanding IC disease pathophysiology.
2014-05-13 | E-GEOD-57560 | biostudies-arrayexpress
Project description:The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) remains incompletely understood. Bladder fibrosis is a significant histopathological feature of IC/BPS, particularly in non-Hunner-type IC (NHIC). Transient receptor potential cation channel subfamily C member 3 (TRPC3) is known to play a crucial role in myocardial and renal fibrosis. This study investigates the involvement of TRPC3 in bladder fibrosis associated with IC/BPS. A rat model of IC/BPS was established using cyclophosphamide (CYP, 50 mg/kg, intraperitoneally, every 3 days for 3 doses). Bulk RNA sequencing was used to identify differentially expressed transient receptor potential (TRP) channel genes in CYP-induced cystitis rats, whereas single-cell RNA sequencing was utilized to pinpoint the cell type predominantly expressing transient receptor potential cation channel subfamily C member 3 (TRPC3) . TRPC3 inhibition was achieved through intraperitoneal injection of Pyrazole 3 (Pyr3, 0.1 mg/kg or 1 mg/kg). Suprapubic mechanical allodynia was assessed using up-down method with von Frey filaments and micturition frequency was assessed by cystometry. The expression of TRPC3 and components of the transforming growth factor beta (TGF-β)/Smad signaling pathway (TGF-β, p-Smad2, and p-Smad3) in the bladder was analyzed by Western blot. Bladder fibrosis was assessed through Masson’s staining and detection of fibrosis markers (Vimentin, Collagen I, and Collagen III) using Western blot. The RNA and protein expression of TRPC3 was up-regulated in CYP-induced cystitis rats. TRPC3 inhibition led to significant improvements in suprapubic mechanical allodynia and reduced micturition frequency in CYP-induced cystitis rats. Western blot analyses revealed that markers of bladder fibrosis (Vimentin, Collagen I, and Collagen III) were markedly upregulated in CYP-induced cystitis rats. Masson’s staining showed an increased area of collagen fibers. Additionally, inhibition of TRPC3 resulted in significant downregulation of the TGF-β/Smad signaling pathway (TGF-β, p-Smad2, and p-Smad3) in CYP-induced cystitis rats. TRPC3 activation contributes to bladder fibrosis in IC/BPS. Inhibition of TRPC3 ameliorates suprapubic mechanical allodynia and micturition frequency in CYP-induced cystitis rats by downregulating the TGF-β/Smad pathway. TRPC3 represents a potential therapeutic target for managing bladder fibrosis in IC/BPS.
2025-03-31 | GSE293339 | GEO
Project description:Interstitial cystitis (IC), a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. The ultimate goal is the development of a diagnostic assay for IC on a molecular level. By cystoscopic examination, IC can be classified into an ulcerative and a non-ulcerative subtype. To better understand this debilitating disease on a molecular level, a comparative gene expression profile of bladder biopsies from patients with ulcerative IC and control patients has been performed. Candidate marker genes for ulcerative IC were identified.
2009-05-01 | GSE11783 | GEO
Project description:To comprehensively understand the biological significance behind different grades of bladder cancer, we screened samples of different grades of bladder cancer and glandular cystitis from three patients for single-cell sequencing. In this study, We found that N-Glycan biosynthesis pathway was activated in high-grade bladder cancer while TNF-related pathway was activated in cystitis glandularis. More importantly, We discovered that N-Glycan biosynthesis is a potential target by cell assay and inhibition of this pathway may contribute to the treatment of bladder cancer.
2022-04-13 | GSE190888 | GEO
Project description:Interstitial cystitis (IC) is a progressive chronic bladder disease with an increasing incidence. Today, IC is diagnosed by subjective symptoms in combination with cystoscopic and histologic evidence. The ultimate goal is the development of a diagnostic assay for IC on a molecular level. A comparative gene expression profile of bladder biopsies from patients with IC and control patients identified candidate marker genes for IC. Experiment Overall Design: Five IC patients and six control patients ('healthy') have been selected for the study. All IC patients had Hunner's ulcers and, with the exception of one person, also glomerulations, whereas the control group did not show these cystoscopic findings. From each IC patient two biopsies have been taken, one from an ulcerated area of the bladder ('ulcus'), and one from an area that macroscopically looked 'normal', 'not-inflamed' or not hyperemic ('ni'). One 'ni' sample has been excluded from the study because it had an expression pattern similar to the healthy controls.
2009-05-14 | E-GEOD-11783 | biostudies-arrayexpress