Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Zeng, Jing; Ekman, Mari; Jiang, Chonghe; Uvelius, Bengt; Swärd, Karl

doi:10.1016/j.ejphar.2015.05.037

Cited by 8 publications

(5 citation statements)

References 43 publications

(34 reference statements)

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“…One example is the limited effect of β 3 -adrenoceptor agonists in patients with outlet obstruction [ 44 , 45 ]. Our obstructed rat model has a decreased mRNA level for β 3 -adrenocceptors, and in vitro, the relaxing effect of β 3 -adrenoceptor agonists on pre-contracted rat detrusor strips is almost non-existent [ 46 ]. As the mRNA for β 3 -adrenoceptors is normalized in the de-obstructed bladders, one would expect a more favorable effect on DO by β 3 -adrenoceptor agonists in such bladders.…”

Section: Discussionmentioning

confidence: 99%

Molecular and Morphological Characteristics of the De-Obstructed Rat Urinary Bladder—An Update

Uvelius

Andersson

2022

IJMS

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Many patients with outlet obstruction secondary to prostatic enlargement have lower urinary tract symptoms (LUTSs) and an increased frequency of micturition. The standard treatment is transurethral resection of the prostate (TURP), which alleviates obstruction and symptoms. However, after TURP, 20–40 percent of patients continue to experience LUTSs. The aim of the present study in rats was to identify the mechanisms that do not normalize after the removal of the obstruction and that could explain the persisting symptoms. We had microarray data from control, obstructed, and de-obstructed female rat bladders, which made it possible to study 14,553 mRNA expressions. We also had a bank of electron micrographs from similar detrusors. Microarrays: There were significant differences between the control and obstructed bladders for 1111 mRNAs. The obstructed and de-obstructed bladders differed significantly for 1059 mRNAs. The controls and the de-obstructed bladders differed significantly for 798 mRNAs. We observed many mRNAs that were increased in the obstructed bladder and then decreased to control levels after de-obstruction, and many mRNAs that were decreased in the obstructed bladder and then increased following de-obstruction. mRNAs that were significantly higher or lower in the de-obstructed bladder than in the control bladder were also found. Ultrastructure: The detrusor cells in the obstructed bladders had cross-sectional areas that were much larger than those in the controls. The control cells had smooth outlines and similar cross-sectional areas. The de-obstructed detrusor cells had larger cross-sectional areas than the controls, as well as corrugated surfaces. The cell areas varied, suggesting that the shrinkage of the de-obstructed cells was not even. We did not find any points of contact of the gap junction plaque type between the detrusor cells. There were abundant finger-like processes between the detrusor cells in the obstructed and in de-obstructed bladders, which were only occasionally found in the control detrusors. They are the only possible localization for gap junction channels. The de-obstructed rat bladder is not an organ with properties intermediate between those of the control and obstructed bladders. Instead, de-obstructed bladders have gene expressions, morphologies, and functional properties of the individual cells and their organization, which make them distinctly different from both control and obstructed bladders.

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Section: Discussionmentioning

confidence: 99%

Molecular and Morphological Characteristics of the De-Obstructed Rat Urinary Bladder—An Update

Uvelius

Andersson

2022

IJMS

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“…Following BOO in rats there are non-uniform changes in bladder membrane receptors (55). Some receptors are upregulated and can be associated with increased agonist responses whereas other can be down-regulated leading to decreased responses.…”

Section: Membrane Receptorsmentioning

confidence: 99%

Changes in the rat urinary bladder after the relief of outflow obstruction – tracing targets for treatment of persistent symptoms in patients

Andersson

Uvelius²

2022

Front. Urol.

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Studies on patients with bladder outflow obstruction who have undergone surgery for benign prostatic hyperplasia, successfully relieving the obstruction, have revealed a persistence of storage symptoms associated with detrusor overactivity (DO) in 20% to 40% of patients. To study the underlying mechanisms, we have used a common rat model of obstruction/de-obstruction, assuming that non-voiding contractions can be used as a surrogate parameter for DO in humans. Using microarray analysis and electron microscopic images from obstructed and de-obstructed bladder tissue we have tried to identify changes that could serve as a basis for the search of new targets for drugs. Even if voiding function is rapidly normalized after release of outflow obstruction and many of the morphological changes are reversed, the microarray analysis revealed that the de-obstructed rat bladder has gene expressions, structural, and functional properties that make it distinctly different from both control and obstructed bladders. We suggest that whole bladder arrays can be used for identifying cellular mechanisms that could be targets for drugs meant for treatment of persistent DO and LUTS after de-obstruction. Based on available array information for some membrane receptors and morphologic structures with corresponding changes in bladder function, it seems worthwhile to re-assess the development potential for e.g., endothelin receptor antagonists, purinergic receptor antagonists and Rho-kinase inhibitors.

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“…In an additional study, a microarray analysis detected an increase in LGR6 in a rat model of BOO but with no context of possible function. 32 Recently, we expounded on a possible role for Annexin-A1 in treating BOO using a rat model. 33 In those studies, we demonstrated the presence of all six SPM receptors in the rat bladder.…”

Section: Introductionmentioning

confidence: 99%

Specialized pro-resolution mediators in the bladder: Receptor expression and recovery of bladder function from cystitis

Hughes

Allkanjari

Odom

et al. 2022

Exp Biol Med (Maywood)

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Inflammation is a central process in most benign bladder disorders, and its control is a delicate balance between initiating factors and resolving factors. While recent discoveries have shown a central role for the NLRP3 inflammasome in initiation, the resolving pathways remain unexplored. Resolution is controlled by specialized pro-resolution mediators (SPMs) functioning through seven receptors (six in rodents). Here we demonstrate expression of all seven in humans (six in mice) through immunocytochemistry. Expression was universal in urothelia with most also expressed in smooth muscle. We next explored the therapeutic potential of three SPMs; Resolvin E1 (RvE1), Maresin 1 (MaR1), and Protectin D1 (PD1). SPMs promote epithelial wound/barrier repair and RvE1 triggered dose-dependent wound closure in urothelia in vitro (scratch assay) (EC90 = 12.5 nM). MaR1 and PD1 were equally effective at this concentration. In vivo analyses employed a cyclophosphamide (CP) model of bladder inflammation (Day 0-CP [150 mg/kg], Day 1 to 3 SPM [25 µg/kg/day], Day 4 – analysis). All three SPMs reduced bladder inflammation (Evans blue) and bladder weights to control levels. Effects of RvE1 were also examined by urodynamics. CP decreased void volume, increased frequency and decreased bladder capacity while RvE1 restored values to control levels. Finally, SPMs reduce fibrosis and RvE1 reduced urothelial expression of TGF-β and collagen I to control values. Together these results expand the known SPMs active in the bladder tissue and provide promising therapeutic targets for controlling inflammation in a wide variety of inflammation-associated benign bladder diseases.

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Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Cited by 8 publications

References 43 publications

Molecular and Morphological Characteristics of the De-Obstructed Rat Urinary Bladder—An Update

Molecular and Morphological Characteristics of the De-Obstructed Rat Urinary Bladder—An Update

Changes in the rat urinary bladder after the relief of outflow obstruction – tracing targets for treatment of persistent symptoms in patients

Specialized pro-resolution mediators in the bladder: Receptor expression and recovery of bladder function from cystitis

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