Effect of Sulforaphane on Bladder Compliance in a Rat Model of Partial Bladder Outlet Obstruction

Liu, Chong; Wan, Xiang; Gu, Meng; Chen, Yanbo; Cai, Zhixiang; Zhou, Juan; Chen, Qi; Wang, Zhong

doi:10.1155/2019/6026719

Cited by 5 publications

(4 citation statements)

References 21 publications

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“…Many studies have indicated that ECM deposition increases after pBOO, leading to decreased bladder compliance. 22 Moreover, in an investigation of the impact of Thbs1 on the ECM, normal human urinary epithelial cells were stimulated with TGF-β1 to establish an in vitro fibrosis model. 23 In this study, we found that Fn and MMPs were highly expressed in SV-HUC-1 cells induced by TGF-β1.…”

Section: Discussionmentioning

confidence: 99%

Targeting Thbs1 reduces bladder remodeling caused by partial bladder outlet obstruction via the FGFR3/p‐FGFR3 pathway

Long,

Yang,

Yang

et al. 2023

Neurourology and Urodynamics

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BackgroundPartial bladder outlet obstruction (pBOO) may lead to bladder remodeling, including fibrosis and extracellular matrix (ECM) deposition. Despite the extensive research on the mechanisms underlying pBOO, potential therapeutic targets for the treatment of pBOO require further research. Dysregulated expression of thrombospondin‐1 (Thbs1) has been reported in various human fibrotic diseases; however, its relationship with pBOO remains unclear.AimsInvestigate the effects of Thbs1 on bladder remodeling caused by pBOO.MethodsWe established a pBOO model in Sprague–Dawley rats and performed urodynamic analyses to estimate functional changes in the bladder, validated the histopathological changes in the bladder by using haematoxylin–eosin and Masson's trichrome staining, identified key target genes by integrating RNA sequencing (RNA‐seq) and bioinformatics analyses, validated the expression of related factors using Western blot analysis and RT‐qPCR, and used immunofluorescence staining to probe the potential interaction factors of Thbs1.ResultsUrodynamic results showed that pressure‐related parameters were significantly increased in rats with pBOO. Compared with the sham group, the pBOO group demonstrated significant increases in bladder morphology, bladder weight, and collagen deposition. Thbs1 was significantly upregulated in the bladder tissues of rats with pBOO, consistent with the RNA‐seq data. Thbs1 upregulation led to increased expression of matrix metalloproteinase (MMP) 2, MMP9, and fibronectin (Fn) in normal human urinary tract epithelial cells (SV‐HUC‐1), whereas anti‐Thbs1 treatment inhibited the production of these cytokines in TGF‐β1‐treated SV‐HUC‐1. Further experiments indicated that Thbs1 affected bladder remodeling in pBOO via the fibroblast growth factor receptor 3 (FGFR3) pathway.ConclusionsThbs1 plays a crucial role in bladder remodeling caused by pBOO. Targeting Thbs1 might alleviate ECM damage. Mechanistically, Thbs1 may function via the FGFR signaling pathway by regulating the FGFR3 receptor, identified as the most relevant disease target of pBOO, and FGF2 may be a mediator. These findings suggest that Thbs1 plays a role in BOO development and is a therapeutic target for this condition.

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Section: Discussionmentioning

confidence: 99%

Targeting Thbs1 reduces bladder remodeling caused by partial bladder outlet obstruction via the FGFR3/p‐FGFR3 pathway

Long,

Yang,

Yang

et al. 2023

Neurourology and Urodynamics

View full text Add to dashboard Cite

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“…Functional enrichment analysis in the present study revealed that extracellular matrix-related functions were also significantly activated. Collagen I and III are the main factors of bladder compliance ( 45 ). Once collagen is heavily deposited in the bladder wall, elastin becomes relatively reduced, leading to thicker bladder walls, decreased smooth muscle function, reduced bladder compliance and even bladder fibrosis ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Urinary exosomal vitronectin predicts vesicoureteral reflux in patients with neurogenic bladders and spinal cord injuries

Cai

Zeng

et al. 2021

Exp Ther Med

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Neurogenic bladder (NGB) is an important complication of urinary tract dysfunction after spinal cord injury (SCI). However, using urodynamics and urography to guide therapy remains invasive and complicated. Therefore, the present study aimed to identify potential noninvasive biomarkers from urinary exosomes that can facilitate diagnosis and guide prognosis of patients with NGB subsequent to SCI. Urinary exosomes were isolated, and their proteome profile was analyzed by mass spectrometry. Transmission electron microscopy and Nanoparticle Tracking Analysis confirmed the size and morphological characteristics of urinary exosomes. In addition, bioinformatics analysis and parallel reaction monitoring (PRM) were used to screen candidate biomarkers. The selected biomarkers were validated using western blotting and ELISA. Mass spectrometry identified 134 upregulated proteins and 99 downregulated proteins between the vesicoureteral reflux (VUR) and non-VUR groups. A total of 18 candidate proteins were selected for PRM validation, but only vitronectin (VTN) and α-1 type I collagen (COL1A1) demonstrated significant differences. In the validation experiments using western blotting and ELISA, VTN was exclusively highly expressed in VUR patients compared with non-VUR patients. However, the ELISA results of COL1A1 revealed no significant difference when a larger sample size was used. Furthermore, a receiver operating characteristic curve of ELISA-based VTN demonstrated an area under the curve of 0.795 and 80% sensitivity at a threshold set to give 82.9% specificity. Collectively, these results suggested that VTN in urinary exosomes may be used as a biomarker to predict the progression and guide the prognosis of NGB.

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“…In addition, Frontiers in Pharmacology frontiersin.org they found that SFN could alleviate pBOO-induced bladder injury by activating the Nrf2-ARE pathway, increasing the activity of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT) to reduce oxidative stress, and lowering the B cell lymphoma 2 associated X protein (Bax)/B cell lymphoma 2 (bcl-2) ratio to inhibit apoptosis (Liu et al, 2016). In Liu et al's subsequent in vivo study (Liu et al, 2019), through treating BOO rat models with 0.5 mg/kg/day of SFN, they found that bladder compliance in BOO rats was significantly reduced. Further research found that SFN improved bladder compliance by upregulating matrix metalloproteinases-1 (MMP-1) and downregulating tissue inhibitors of metalloproteinases-1 (TIMP-1) expression.…”

Section: Sulforaphane and Bladder Outlet Obstruction: Bladder Protectionmentioning

confidence: 99%

Sulforaphane and bladder cancer: a potential novel antitumor compound

Zuo,

Chen,

Liao

et al. 2023

Front. Pharmacol.

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Bladder cancer (BC) is a common form of urinary tract tumor, and its incidence is increasing annually. Unfortunately, an increasing number of newly diagnosed BC patients are found to have advanced or metastatic BC. Although current treatment options for BC are diverse and standardized, it is still challenging to achieve ideal curative results. However, Sulforaphane, an isothiocyanate present in cruciferous plants, has emerged as a promising anticancer agent that has shown significant efficacy against various cancers, including bladder cancer. Recent studies have demonstrated that Sulforaphane not only induces apoptosis and cell cycle arrest in BC cells, but also inhibits the growth, invasion, and metastasis of BC cells. Additionally, it can inhibit BC gluconeogenesis and demonstrate definite effects when combined with chemotherapeutic drugs/carcinogens. Sulforaphane has also been found to exert anticancer activity and inhibit bladder cancer stem cells by mediating multiple pathways in BC, including phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), nuclear factor kappa-B (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), zonula occludens-1 (ZO-1)/beta-catenin (β-Catenin), miR-124/cytokines interleukin-6 receptor (IL-6R)/transcription 3 (STAT3). This article provides a comprehensive review of the current evidence and molecular mechanisms of Sulforaphane against BC. Furthermore, we explore the effects of Sulforaphane on potential risk factors for BC, such as bladder outlet obstruction, and investigate the possible targets of Sulforaphane against BC using network pharmacological analysis. This review is expected to provide a new theoretical basis for future research and the development of new drugs to treat BC.

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Effect of Sulforaphane on Bladder Compliance in a Rat Model of Partial Bladder Outlet Obstruction

Cited by 5 publications

References 21 publications

Targeting Thbs1 reduces bladder remodeling caused by partial bladder outlet obstruction via the FGFR3/p‐FGFR3 pathway

Targeting Thbs1 reduces bladder remodeling caused by partial bladder outlet obstruction via the FGFR3/p‐FGFR3 pathway

Urinary exosomal vitronectin predicts vesicoureteral reflux in patients with neurogenic bladders and spinal cord injuries

Sulforaphane and bladder cancer: a potential novel antitumor compound

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