Comparative RNA-sequencing analysis of the prostate in a mouse model of benign prostatic hyperplasia with bladder outlet obstruction
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE218403 | GEO | 2023/11/15
REPOSITORIES: GEO
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Project description:BackgroundUrothelial cells release ATP into the urine in response to bladder stretch. Urinary ATP concentration in benign prostatic hyperplasia (BPH) patients was higher compared with asymptomatic controls. In this study, we aimed to explore the possibility that the urinary ATP level could be a non-invasive biomarker for bladder outlet obstruction (BOO) and its severity in BPH patients.MethodsWe included 117 BPH patients who underwent urodynamic studies and 109 asymptomatic controls. Urine samples at normal desire (from patients and controls), instilled fluids at maximum cystometric capacity (capacity fluid), and voided fluids during a pressure-flow study (only from patients) were collected. The ATP concentration in collected samples was measured using a luciferin-luciferase bioluminescence assay and normalized to urine creatinine (ATP/Cr). The degree of BOO was quantified using the BOO index (BOOI). Correlation between urodynamic parameters and urinary ATP concentration was analyzed in BPH patients.ResultsUrinary ATP concentration of BPH patients was significantly higher compared with controls (P<0.001). For BPH patients, a significant positive correlation was found between urinary ATP concentration and BOOI (P<0.0001). Although BPH patients with detrusor overactivity or a history of acute urinary retention had increased urinary ATP, a significant positive correlation between ATP and BOOI was also observed in these patients. When BOOI >40 was set as a cutoff point to differentiate BOO from non-BOO patients, the area under the receiver operating characteristic (ROC) curve was 0.77 (P<0.001).ConclusionsBPH patients with BOO released higher amounts of ATP into the urine. Urinary ATP can be used as a non-invasive biomarker of BOO, and its level may also have a predictive value for the degree of obstruction.
| S-EPMC7215044 | biostudies-literature
Project description:Analysis of gene expression in prostatic tissue from BPH patients with and without SRD5A2 gene methylation. The hypothesis is that BPH patients with DNA methylation of the SRD5A2 gene promoter have impaired conversion of testosterone to dihydrotestosterone, and therefore may use an alternative signaling pathway for prostatic tissue growth. Here, we compare gene expression profiles of SRD5A2-methylated vs. unmethylated prostatic tissue to nominate alternative biological pathways relevant in each molecular subtype of BPH.
2017-10-01 | GSE101486 | GEO
Project description:Background:We report a rare case of acute pulmonary embolism (PE) induced by urinary retention and bladder distention with benign prostatic hyperplasia (BPH). Case report:A 76-year-old male with BPH presented to the hospital with anuria of 24 h duration and abdominal distention. Physical examination revealed tenderness and distention of the lower abdomen and a swollen right leg. Echocardiography after urethral catheterization showed a large free-floating thrombus traversing back and forth through the tricuspid orifice. Computed tomographic angiography demonstrated filling defects at the level of the right inter lobar pulmonary artery and the segmental branches of both pulmonary arteries, indicating acute PE. The patient was treated with heparin and warfarin for three weeks to ensure the resolution of the pulmonary embolus. After the resolution of all symptoms, the patient was discharged without further complication. Conclusion:This case suggested that a distended bladder is a potential risk factor for the development of deep vein thrombosis and PE.
| S-EPMC6265422 | biostudies-literature
Project description:Comparative RNA-sequencing analysis of the prostate in a mouse model of benign prostatic hyperplasia with bladder outlet obstruction
| PRJNA903775 | ENA
Project description:We aim to find the risk factors that influence the formation of bladder calculi in patients with benign prostate hyperplasia (BPH) and to reduce the surgical intervention related to bladder calculi.Between January 2015 and October 2016, 332 patients with BPH underwent surgical therapy were retrospectively evaluated. Patients with BPH were categorized into 2 groups: 94 patients with bladder calculi in group 1 and 238 patients without bladder calculi in group 2. Medical history, age, body mass index (BMI), total prostate specific antigen, total prostate volume (TPV), International Prostate Symptom Score (IPSS), intravesical prostatic protrusion (IPP), urodynamic parameters, and urine culture were compared between groups.There was no significant difference in the age, BMI, peak flow rate, and total IPSS between groups. TPV, total prostate specific antigen, and duration of BPH were significantly lower in group 1 than those in group 2. In addition, IPP was significantly higher in group 1 than group 2 (P < .001). Besides, after exclusion of patients with urinary retention and indwelling catheter, group 1 associated with a significantly higher preoperative positive rate of urine culture than that of group 2 (P = .046). Multivariate analysis indicated that IPP was a significant independent risk factor for the presence of bladder calculi.The incidence of bladder calculi in patients with BPH was proved to be closely associated with preoperative positive urine culture and longer IPP in our study. Furthermore, the IPP was presented to be an independent risk factor for the formation of bladder calculi. And early antibacterial therapy of urinary tract infection (UTI) may help to prevent the presence of bladder calculi in patients with BPH.
| S-EPMC5556223 | biostudies-other
Project description:ObjectivesOveractive bladder (OAB) symptoms are often encountered in patients after transurethral resection of the prostate (TUR-P) or transurethral incision of the prostate (TUI-P) for benign prostatic obstruction (BPO). Either antimuscarinics or β-3 agonist has been found effective in relieving OAB symptoms. However, urologists usually do not prescribe such medication immediately after TUR-P or TUI-P to avoid an increase in postvoid residual and risk of urinary tract infection. If OAB medication can be used and adverse events (AEs) can be reduced to minimum, patients' quality of life after bladder outlet obstruction surgery could be improved. This study compared the safety and efficacy between solifenacin and mirabegron in men undergoing TUR-P or TUI-P.Materials and methodsThis prospective, randomized trial compared the safety and efficacy of OAB medication on the reduction in Urgency Severity Score (USS), OAB Symptoms Score (OABSS), International Prostate Symptom Score, and urgency urinary incontinence episodes in men with BPO undergoing surgical intervention. All patients could void smoothly after catheter removal and were randomly received daily solifenacin 5 mg, mirabegron 50 mg, or no interventions for 4 weeks. At 2 and 4 weeks postoperatively, participants' OAB symptoms and AEs were evaluated.ResultsA total of 57 men were enrolled in this study with a mean age of 70.8 ± 6.1 years. At 2 weeks postoperatively, USS (1.56 ± 1.72 vs. 2.39 ± 1.72 vs. 2.26 ± 1.73, P < 0.011) and OABSS (5.33 ± 3.65 vs. 7.67 ± 4.19 vs. 8.58 ± 4.31, P < 0.000) were significantly reduced in patients taking solifenacin, mirabegron, or control, respectively. Two patients in the solifenacin group developed urinary retention. However, the changes of variables at 4 weeks postoperatively were insignificant among the three groups.ConclusionSolifenacin and mirabegron are two different drug classes both equally effective in treating immediate OAB symptoms after TUR-P or TUI-P. However, OAB symptoms could be relieved at 4 weeks without any medication. Considering AEs, β-3 agonist has a more favorable safety profile than antimuscarinics.
| S-EPMC10683516 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is characterized by increased tissue mass in the transition zone of the prostate, which leads to obstruction of urine outflow and significant morbidity in the majority of older men. Plasma markers of oxidative stress are increased in men with BPH but it is unclear whether oxidative stress and/or oxidative DNA damage are causal in the pathogenesis of BPH.Levels of 8-OH deoxyguanosine (8-OH dG), a marker of oxidative stress, were measured in prostate tissues from normal transition zone and BPH by ELISA. 8-OH dG was also detected in tissues by immunohistochemistry and staining quantitated by image analysis. Nox4 promotes the formation of reactive oxygen species. We therefore created and characterized transgenic mice with prostate specific expression of Nox4 under the control of the prostate specific ARR2PB promoter.Human BPH tissues contained significantly higher levels of 8-OH dG than control transition zone tissues and the levels of 8-OH dG were correlated with prostate weight. Cells with 8-OH dG staining were predominantly in the epithelium and were present in a patchy distribution. The total fraction of epithelial staining with 8-OH dG was significantly increased in BPH tissues by image analysis. The ARR2PB-Nox4 mice had increased oxidative DNA damage in the prostate, increased prostate weight, increased epithelial proliferation, and histological changes including epithelial proliferation, stromal thickening, and fibrosis when compared to wild type controls.Oxidative stress and oxidative DNA damage are important in the pathogenesis of BPH.
| S-EPMC5469601 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) are common in older men and can contribute to lower urinary tract symptoms that significantly impact quality of life. Few existing models of BOO and BPH use physiological levels of hormones associated with disease progression in humans in a genetically manipulable organism. We present a model of BPH and BOO induced in mice with testosterone (T) and 17?-estradiol (E(2)). Male mice were surgically implanted with slow-releasing sc pellets containing 25 mg T and 2.5 mg E(2) (T+E(2)). After 2 and 4 months of hormone treatment, we evaluated voiding patterns and examined the gross morphology and histology of the bladder, urethra, and prostate. Mice treated with T+E(2) developed significantly larger bladders than untreated mice, consistent with BOO. Some mice treated with T+E(2) had complications in the form of bladder hypertrophy, diverticula, calculi, and eventual decompensation with hydronephrosis. Hormone treatment caused a significant decrease in the size of the urethral lumen, increased prostate mass, and increased number of prostatic ducts associated with the prostatic urethra, compared with untreated mice. Voiding dysfunction was observed in mice treated with T+E(2), who exhibited droplet voiding pattern with significantly decreased void mass, shorter void duration, and fewer sustained voids. The constellation of lower urinary tract abnormalities, including BOO, enlarged prostates, and voiding dysfunction seen in male mice treated with T+E(2) is consistent with BPH in men. This model is suitable for better understanding molecular mechanisms and for developing novel strategies to address BPH and BOO.
| S-EPMC3473198 | biostudies-literature
Project description:BackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.
| S-EPMC7485377 | biostudies-literature
Project description:BPH is the most prevalent prostatic condition in aging dogs. Nevertheless, clinical diagnosis and management remain inconsistent. This study employed in-solution digestion coupled with nano-liquid chromatography tandem mass spectrometry to assess serum proteome profiling of dogs with BPH and those dogs after castration. Male dogs were divided into two groups; control and BPH groups. In the BPH group, each dog was evaluated at two time points: Day 0 (BF subgroup) and Day 30 after castration (AT subgroup). In the BF subgroup, three proteins were significantly upregulated and associated with dihydrotestosterone: solute carrier family 5 member 5, tyrosine-protein kinase, and FRAT regulator of WNT signaling pathway 1. Additionally, the overexpression of polymeric immunoglobulin receptors in the BF subgroup hints at its potential as a novel protein linked to the BPH development process. Conversely, alpha-1-B glycoprotein (A1BG) displayed significant downregulation in the BF subgroup, suggesting A1BG's potential as a predictive protein for canine BPH. Finasteride was associated with increased proteins in the AT subgroup, including apolipoprotein C-I, apolipoprotein E, apolipoprotein A-II, TAO kinase 1, DnaJ homolog subfamily C member 16, PH domain and leucine-rich repeat protein phosphatase 1, neuregulin 1, and pseudopodium enriched atypical kinase 1. In conclusion, this pilot study highlighted alterations in various serum proteins in canine BPH, reflecting different pathological changes occurring in this condition. These proteins could be a source of potential non-invasive biomarkers for diagnosing this disease.
| S-EPMC10740436 | biostudies-literature