Can bladder fibrosis in congenital urinary tract obstruction be reversed?

Lu, Yutao; Tingskov, Stine Julie; Djurhuus, Jens Christian; Nørregaard, Rikke; Olsen, Lars Henning

doi:10.1016/j.jpurol.2017.08.013

Cited by 21 publications

(17 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While bladder fibrosis accompanies the aging bladder, bladder outlet obstruction can also lead to fibrosis and DUA. A recent review pondered the question of whether fibrosis, after it has occurred, can be reversed [ 24 ]. Bladder fibrosis occurred when there was supraphysiologic repetitive bladder strain that triggered downstream activation of pro-fibrotic pathways including transforming growth factor β (TGFβ) and hypoxia inducible factor.…”

Section: Drug Therapymentioning

confidence: 99%

New therapeutic directions to treat underactive bladder

Chai

Kudze

2017

Investig Clin Urol

View full text Add to dashboard Cite

Underactive bladder (UAB) is a term used to describe a constellation of symptoms that is perceived by patients suggesting bladder hypocontractility. Urodynamic measurement that suggest decreased contractility of the bladder is termed detrusor underactivity (DUA). Regulatory approved specific management options with clinically proven ability to increase bladder contractility do not currently exist. While DUA specific treatments presumably will focus on methods to increase efficiency of bladder emptying capability relying on augmenting the motor pathway in the micturition reflex, other approaches include methods to augment the sensory (afferent) contribution to the micturition reflex which could result in increased detrusor contractility. Another method to induce more efficient bladder emptying could be to induce relaxation of the bladder outlet. Using cellular regenerative techniques, the detrusor smooth muscle can be targeted so the result is to increase detrusor smooth muscle function. In this review, we will cover areas of potential new therapies for DUA including: drug therapy, stem cells and regenerative therapies, neuromodulation, and urethral flow assist device. Paralleling development of new therapies, there also needs to be clinical studies performed that address how DUA relates to UAB.

show abstract

Section: Drug Therapymentioning

confidence: 99%

New therapeutic directions to treat underactive bladder

Chai

Kudze

2017

Investig Clin Urol

View full text Add to dashboard Cite

show abstract

“…It is well known that bladder fibrosis eventually decreases bladder compliance of NPB, which then aggravates upper urinary tract drainage, eventually producing hydronephrosis and finally, renal impairment 4 . Currently, there are no effective therapies to reverse these fibrotic changes once they begin 5 . Therefore, it is important to find a medication that prevents fibrosis associated with NPB with the ultimate aim of preserving kidney function.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have shown that Ang II can promote the occurrence of fibrosis in some organs of the body by binding AT1, further promoting transforming growth factor β1 (TGFβ1) synthesis 6,8,9 ; TGFβ1 was found to be a key molecule in the development of fibrosis of most tissues in the human body, as TGFβ1 binds to serine/threonine kinase receptors on the cell surface that phosphorylate intracellular Smad2/3 transcription factors to induce collagen production leading to increased deposition of collagen in tissues 10,11 . TGFβ1/smads signaling was also found to be one of the mechanisms of bladder fibrosis development in cases of bladder outlet obstruction (BOO) 5 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Losartan prevents bladder fibrosis and protects renal function in rat with neurogenic paralysis bladder

Wen

et al. 2021

Neurourology and Urodynamics

View full text Add to dashboard Cite

Aims: To investigate the effect of losartan on preventing bladder fibrosis and protecting renal function in rats with neurogenic paralysis bladder (NPB). Materials and Methods: Rats were assigned to the transecting spinal nerves group (TSNG), transecting spinal nerves + losartan group (LSTG), and control group (CG). On Day 32 postsurgery, bladder capacity (BC), bladder compliance (ΔC), bladder leakage pressure (P ves.leak) of TSNG and LSTG while BC, ΔC, and bladder threshold pressure (P ves.thre) of CG were measured by cystometry in each cohort. Renal function and the expression quantity of Angiotensin Ⅱ (Ang II) in blood were detected, in addition Ang II, Ang II Type 1 receptor (AT1), transformation growth factor β1 (TGFβ1), Collagen Ⅲ, and collagen fibrin in the bladder tissue were detected too. Results: ΔC in TSNG and LSTG decreased significantly compared to the CG. P ves.leak in TSNG and LSTG were significantly higher than P ves.thre in CG. Renal function of both TSNG and LSTG decreased significantly compared with the CG, but renal function in LSTG was better than in TSNG. Ang Ⅱ in blood and bladder tissue in TSNG and LSTG increased significantly compared with CG. AT1 was expressed in the bladder tissue of all rats. The TGFβ1, Collagen Ⅲ, and collagen fibrin expression level increased significantly in TSNG compared with LSTG and CG, while these levels were not significantly different between CG and LSTG. Conclusion: Losartan might prevent NPB fibrosis by stopping the upregulated signaling of Ang II/AT1/TGFβ1 and consequently may reduce kidney damage from occurring.

show abstract

“…TGF-β1 plays an important role in inflammation and fibrosis, and induces hypertrophic changes in cellular function and tissue morphology. [11][12][13] Knowledge of the pathophysiology of organ fibrosis has led to research on several antifibrotic drugs to treat urethral stricture ( Figure 1). Docetaxel inhibits the formation of urethral stricture by inhibiting the formation of fibrosis and collagen coagulation.…”

Section: Introductionmentioning

confidence: 99%

The effects of docetaxel and/or captopril in expression of TGF-β1, MMP-1, CTGF, and PAI-1 as markers of anterior urethral stricture in an animal model

Kurniawan

Soesatyo

Aryandono

2020

Therapeutic Advances in Urology

View full text Add to dashboard Cite

Background: Treatment of urethral trauma is currently done after urethral stricture occurs. Stricture therapy after occurrence gives unsatisfactory success rates. Several genes, such as transforming growth factor beta 1 (TGF-β1), matrix metalloproteinase 1 (MMP-1), connective tissue growth factor (CTGF), and plasminogen activator inhibitor 1 (PAI-1), have a proven role in urethral stricture development. The purpose of this study was to assess the effect docetaxel and/or captopril on the RNA expression of those genes. Methods: The subjects of this research were 26 male New Zealand rabbits aged 230 ± 20 days weighing 4–5 kg that underwent urethral rupture by endoscopic resection under anesthetized conditions. Subjects were divided into five groups; control, stricture, captopril (captopril 0.05 mg/rabbit/day), docetaxel (docetaxel 0.1 mg/rabbit/day), and docetaxel-captopril (docetaxel 0.1 mg/rabbit/day and captopril 0.05 mg/rabbit/day). Each group consisted of 4–6 rabbits. Each rabbit received a water-soluble transurethral gel containing drug according to its group for 28 days. After the treatment period, rabbits were sacrificed with 200 mg Pentothal, and the corpus spongiosum was then prepared for real-time PCR examination. Results: TGF-β1 RNA expression in the stricture group was statistically different from that in the control, docetaxel and docetaxel-captopril groups ( p = 0.016; p = 0.016; p = 0.004). The stricture group did not exhibit any statistical difference from the captopril group ( p = 0.190). The control group did not show any statistically difference from the captopril, docetaxel, and docetaxel-captopril groups ( p = 0.114; p = 0.190; p = 1.000). Docetaxel-captopril suppresses expression of TGF-β1 RNA most significantly. MMP-1 RNA expression showed no significant differences among groups ( p = 0.827). The docetaxel group and stricture group pair was most significant ( p = 0.247), compared with other pairs of stricture groups in MMP-1 RNA expression. CTGF RNA expression in the stricture group was statistically different from that of control, captopril, docetaxel, and docetaxel-captopril groups ( p = 0.003; p = 0.019; p = 0.005; p = 0.005). The control group did not exhibit any statistically difference from the captopril, docetaxel, and docetaxel-captopril groups ( p = 0.408; p = 0.709; p = 0.695). There was no statistical difference among treatment groups. Docetaxel and docetaxel-captopril groups suppress the most significant expression of CTGF RNA expression. PAI-1 RNA expression in the stricture group differed statistically significantly from the control and docetaxel groups ( p = 0.044; p = 0.016). The stricture group did not show any statistically significant difference from the captopril and docetaxel-captopril groups ( p = 0.763; p = 0.086). The control group did not exhibit any statistical difference with any of the treatment groups ( p = 0.101; p = 0.637; p = 0.669). Conclusion: Docetaxel-captopril gel proved to be able to inhibit RNA expression of TGF-β1 and CTGF significantly. Captopril gel proved to be able to inhibit RNA expression of CTGF significantly. Docetaxel gel proved to be able to inhibit RNA expression of TGF-β1, CTGF, and PAI-1 significantly. There were no differences in MMP-1 expression among all study groups. Longer follow up after therapy discontinuation and greater sample size is needed to determine the therapeutic effect.

show abstract

Can bladder fibrosis in congenital urinary tract obstruction be reversed?

Cited by 21 publications

References 42 publications

New therapeutic directions to treat underactive bladder

New therapeutic directions to treat underactive bladder

Losartan prevents bladder fibrosis and protects renal function in rat with neurogenic paralysis bladder

The effects of docetaxel and/or captopril in expression of TGF-β1, MMP-1, CTGF, and PAI-1 as markers of anterior urethral stricture in an animal model

Contact Info

Product

Resources

About