Gender-dependent bladder response to one-day bladder outlet obstruction

Autor: Kristian Fog-Poulsen, Jens Christian Djurhuus, Rikke Nørregaard, Yutao Lu, L. Henning Olsen
Rok vydání: 2020
Předmět:
Zdroj: Lu, Y, Fog-Poulsen, K, Nørregaard, R, Djurhuus, J C & Olsen, L H 2021, ' Gender-dependent bladder response to one-day bladder outlet obstruction ', Journal of Pediatric Urology, vol. 17, no. 2, pp. 170.e1-170.e10 . https://doi.org/10.1016/j.jpurol.2020.12.026
ISSN: 1873-4898
DOI: 10.1016/j.jpurol.2020.12.026
Popis: 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 Our data indicate that some specific proteins and growth factors were detected as early alterations of tissue which may lead to fibrosis. In addition, the males tended to have more pronounced response than females. However, the causes and consequences of the findings need to be further investigated. Download : Download high-res image (91KB) Download : Download full-size image Summary Fig . Mice 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
Databáze: OpenAIRE