Effects of Prolyl 4-Hydroxylase Inhibitor on Bladder Function, Bladder Hypertrophy and Collagen Subtypes in a Rat Model With Partial Bladder Outlet Obstruction

Urology ◽  
2012 ◽  
Vol 80 (6) ◽  
pp. 1390.e7-1390.e12 ◽  
Author(s):  
Jae Min Chung ◽  
Min Jung Jung ◽  
Sang-Jin Lee ◽  
Sang Don Lee
Keyword(s):  
Rat Model ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Bladder Function ◽  
Partial Bladder Outlet Obstruction

scholarly journals Human Urine-derived Stem Cells Improve Partial Bladder Outlet Obstruction in Rats: Preliminary Data and microRNA-mRNA Expression Profile

2021 ◽  
Author(s):  
Menjiang Tu ◽  
Rui Wang ◽  
Pei Zhu ◽  
Qingqing Wang ◽  
Bishao Sun ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Bladder Outlet Obstruction ◽  
Bioinformatics Analysis ◽  
Therapy Group ◽  
Expression Profiles ◽  
Outlet Obstruction ◽  
Bladder Function ◽  
Detrusor Muscle ◽  
Bladder Tissue ◽  
Partial Bladder Outlet Obstruction

Abstract Background: Partial bladder outlet obstruction (pBOO), a common urological disease, often results in bladder tissue inflammation and remodeling. Human urine-derived stem cells (USCs) have demonstrated therapeutic benefits in various organ injury models. We used a rat model of pBOO to investigate the effect of USCs on bladder function and to explore the miRNA and gene expression profiles in bladder tissue using RNA sequencing.Methods: In total, 18 rats were randomly and evenly assigned to the following three groups: a sham surgery group, a pBOO without USC therapy group, and a pBOO with USC therapy group (subjected to treatment with USCs six times every other week). All rats were subjected to routine urodynamic monitoring. Detrusor muscle strips were analyzed and pathophysiology was assessed. Finally, altered miRNA and mRNA expression profiles of bladder tissue were examined using RNA sequencing and bioinformatics analysis technology.Results: After USC treatment, urodynamic monitoring revealed elevated bladder compliance and maximal voiding pressure, declined end filling pressure and voided volume, and improved detrusor muscle contractility and carbachol sensitivity in pBOO rats. Histology and TUNEL assay revealed reduced collagen deposition and muscle cell apoptosis in bladder tissue. The differential expression of eight miRNAs in pBOO rats was reversed by USC treatment. Bioinformatics analysis helped identify miR-142 and miR-9a as the two largest nodes of differentially expressed miRNAs in the miRNA‑gene interaction network in the USC-treated group. The Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment of multiple significant pathways, including those involved in necroptosis and cytokine-cytokine receptor interactions.Conclusions: This is the first study to reveal the protective effect of USCs on bladder function and bladder remodeling in pBOO rats. The miRNA and mRNA expression levels differed in the bladder of pBOO rats with and without USC treatment. Although the mechanism underlying these effects has not been fully elucidated, necroptosis and cytokine-cytokine receptor interaction-related pathways may be involved.

scholarly journals Differentially Expressed Genes Correlated with Fibrosis in a Rat Model of Chronic Partial Bladder Outlet Obstruction

Processes ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 2219
Author(s):  
Yuan-Shuo Hsueh ◽  
Hui-Hua Chang ◽  
Shun-Yao Ko ◽  
Yi-Pai Lin ◽  
Wei-Yu Lin
Keyword(s):  
Differentially Expressed Genes ◽  
Rat Model ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Clinical Problem ◽  
Differentially Expressed ◽  
Partial Bladder Outlet Obstruction ◽  
Bladder Weight ◽  
Gene Expression Alterations ◽  
Tgfb Signaling

Chronic partial bladder outlet obstruction (PBOO) is a prevalent clinical problem that may result from multiple etiologies. PBOO may be a secondary condition to various anatomical and functional abnormalities. Bladder fibrosis is the worst outcome of PBOO. However, gene alterations and the mechanism of fibrosis development after PBOO onset are not clear. Therefore, we aimed to investigate gene expression alterations during chronic PBOO. A rat model of PBOO was established and validated by a significant increase in rat bladder weight. The bladder samples were further analyzed by microarray, and differentially expressed genes (DEGs) that are more related to PBOO compared with the control genes were selected. The data showed that 16 significantly upregulated mRNAs and 3 significantly downregulated mRNAs are involved in fibrosis. Moreover, 13 significantly upregulated mRNAs and 12 significantly downregulated mRNAs are related to TGFB signaling. Twenty-two significantly upregulated mRNAs and nine significantly downregulated mRNAs are related to the extracellular matrix. The genes with differential expressions greater than four-fold included Grem1, Thbs1, Col8a1, Itga5, Tnc, Lox, Timp1, Col4a1, Col4a2, Bhlhe40, Itga1, Tgfb3, and Gadd45b. The gene with a differential expression less than a quarter-fold was Thbs2. These findings show the potential roles of these genes in the physiology of PBOO.

scholarly journals Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction

2017 ◽  
Vol 313 (5) ◽  
pp. F1149-F1160 ◽  
Author(s):  
Nao Iguchi ◽  
M. İrfan Dönmez ◽  
Anna P. Malykhina ◽  
Alonso Carrasco ◽  
Duncan T. Wilcox
Keyword(s):  
Bladder Outlet Obstruction ◽  
Target Genes ◽  
Bladder Dysfunction ◽  
Pediatric Population ◽  
Outlet Obstruction ◽  
Bladder Function ◽  
Bladder Pressure ◽  
Partial Bladder Outlet Obstruction

Posterior urethral valves are the most common cause of partial bladder outlet obstruction (PBOO) in the pediatric population. Pathological changes in the bladder developed during PBOO are responsible for long-lasting voiding dysfunction in this population despite early surgical interventions. Increasing evidence showed PBOO induces an upregulation of hypoxia-inducible factors (HIFs) and their transcriptional target genes, and they play a role in pathophysiological changes in the obstructed bladders. We hypothesized that blocking HIF pathways can prevent PBOO-induced bladder dysfunction. PBOO was surgically created by ligation of the bladder neck in male C57BL/6J mice for 2 wk. PBOO mice received intraperitoneal injection of either saline or 17-DMAG (alvespimycin, 3 mg/kg) every 48 h starting from day 1 postsurgery. Sham-operated animals received injection of saline on the same schedule as PBOO mice and served as controls. The bladders were harvested after 2 wk, and basal activity and evoked contractility of the detrusor smooth muscle (DSM) were evaluated in vitro. Bladder function was assessed in vivo by void spot assay and cystometry in conscious, unrestrained mice. Results indicated the 17-DMAG treatment preserved DSM contractility and partially prevented the development of detrusor over activity in obstructed bladders. In addition, PBOO caused a significant increase in the frequency of micturition, which was significantly reduced by 17-DMAG treatment. The 17-DMAG treatment improved urodynamic parameters, including increases in the bladder pressure at micturition and nonvoid contractions observed in PBOO mice. These results demonstrate that treatment with 17-DMAG, a HIF inhibitor, significantly alleviated PBOO-induced bladder pathology in vivo.

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