Summary
Background
Development of bladder fibrosis, loss of compliance, and voiding dysfunction are among
the severe consequences of various lower urinary conditions, for example, bladder
outlet obstruction (BOO), neurogenic bladder, and radiotherapy to the pelvic area.
The bladder remodelling results in significant changes in bladder function and architecture,
and may ultimately be deleterious for kidney function. The molecular signals underlying
pathologic bladder remodelling, as well as the impact of gender, remain poorly understood.
Objective
To investigate the bladder remodelling after one day BOO, whether the remodelling
is different between different bladder sections, and whether genders may affect the
remodelling.
Study design
Thirty male and 30 female C57BL/6NRj mice were randomly divided into Control, Sham
and BOO groups with ten mice per group. A 24-h total urethral obstruction was performed
at the proximal urethra. Histological changes were observed via H&E, trichrome and
immunohistochemistry staining. Harvested bladders were divided into upper and lower
sections for analysis. Protein and gene expression were detected by Western blotting
and qPCR.
Results
No significant changes in bladder wall thickness were observed following BOO, while
increased bladder mass after BOO was found in female mice only. We detected FN and
⍺-SMA upregulation in the male upper bladder segment. Female BOO mice bladders showed
increased α-SMA expression in both bladder segments, but no difference of FN was observed
in either bladder segments. BOO-induced upregulation of TGF-β and Gremlin were detected
in both male and female bladders, while downregulation of BMP-7 was detected only
in male bladders. Furthermore, phosphorylation of both SMAD2/3 and SMAD1/5/9 were
increased in male bladders following BOO, whereas female mice exhibited increased
pSMAD2/3 in the upper and increased pSMAD1/5/9 in the lower bladder segment.
Conclusions
Graphical AbstractMice bladder wall thickness and bladder wet weight changes after acute total bladder
outlet obstruction. A significant increase of bladder weight was detected in female mice compared to
control (P < 0.001) and sham (P = 0.002), while bladder wall thickness in the female
obstruction group was similar to those in the control and sham groups. Bars are mean ± SEM.
No significant differences in bladder wall thickness or bladder weight were found
in the male mice. Each group, n = 3–4. Statistical analysis was performed using One-way
analysis of variance (ANOVA). ∗p < 0.05.
Keywords
Abbreviations:
ALK (activin receptor-like kinase), BMP (bone morphogenetic protein), BSA (bovine serum albumin), BOO (bladder outlet obstruction), EMT (epithelial-to-mesenchymal transition), ECM (extracellular matrix), FN (fibronectin), H&E (Hematoxylin and Eosin staining), IHC (Immunohistochemistry), PBS (phosphate buffered saline), RIPA (radioimmunoprecipitation assay), PCR (polymerase chain reaction), TGF-β (transforming growth factor-beta), α-SMA (alfa-smooth muscle actin)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 02, 2021
Accepted:
December 28,
2020
Received in revised form:
November 22,
2020
Received:
May 18,
2020
Identification
Copyright
© 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
