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Neurourology and Urodynamics Mar 2012The urothelium is a multifunctional tissue that not only acts as a barrier between the vesical contents of the lower urinary tract and the underlying tissues but also... (Review)
Review
The urothelium is a multifunctional tissue that not only acts as a barrier between the vesical contents of the lower urinary tract and the underlying tissues but also acts as a sensory organ by transducing physical and chemical stresses to the attendant afferent nervous system and underlying smooth muscle. This review will consider the nature of the stresses that the urothelium can transduce; the transmitters that mediate the transduction process; and how lower urinary pathologies, including overactive bladder syndrome, painful bladder syndrome and bacterial infections, are associated with alterations to this sensory system. In particular, the role of muscarinic receptors and the TRPV channels system will be discussed in this context. The urothelium also influences the contractile state of detrusor smooth muscle, both through modifying its contractility and the extent of spontaneous activity; potential pathways are discussed. The potential role that the urothelium may play in bladder underactivity is introduced, as well as potential biomarkers for the condition that may cross the urothelium to the urine. Finally, consideration is given to vesical administration of therapeutic agents that influence urinary tract function and how the properties of the urothelium may determine the effectiveness of this mode of delivery.
Topics: Adenosine Triphosphate; Animals; Biomarkers; Humans; Mechanotransduction, Cellular; Muscle Contraction; Muscle Relaxation; Receptors, Muscarinic; TRPV Cation Channels; Urinary Bladder; Urinary Bladder Diseases; Urodynamics; Urothelium
PubMed: 22275289
DOI: 10.1002/nau.22195 -
Nature Reviews. Urology Apr 2016The storage and periodic elimination of urine, termed micturition, requires a complex neural control system to coordinate the activities of the urinary bladder, urethra,... (Review)
Review
The storage and periodic elimination of urine, termed micturition, requires a complex neural control system to coordinate the activities of the urinary bladder, urethra, and urethral sphincters. At the level of the lumbosacral spinal cord, lower urinary tract reflex mechanisms are modulated by supraspinal controls with mechanosensory input from the urothelium, resulting in regulation of bladder contractile activity. The specific identity of the mechanical sensor is not yet known, but considerable interest exists in the contribution of transient receptor potential (TRP) channels to the mechanosensory functions of the urothelium. The sensory, transduction, and signalling properties of the urothelium can influence adjacent urinary bladder tissues including the suburothelial nerve plexus, interstitial cells of Cajal, and detrusor smooth muscle cells. Diverse stimuli, including those that activate TRP channels expressed by the urothelium, can influence urothelial release of chemical mediators (such as ATP). Changes to the urothelium are associated with a number of bladder pathologies that underlie urinary bladder dysfunction. Urothelial receptor and/or ion channel expression and the release of signalling molecules (such as ATP and nitric oxide) can be altered with bladder disease, neural injury, target organ inflammation, or psychogenic stress. Urothelial receptors and channels represent novel targets for potential therapies that are intended to modulate micturition function or bladder sensation.
Topics: Animals; Humans; Muscle, Smooth; Signal Transduction; Transient Receptor Potential Channels; Urinary Bladder; Urinary Bladder Diseases; Urination; Urothelium
PubMed: 26926246
DOI: 10.1038/nrurol.2016.13 -
Oncotarget Oct 2016Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular glycoprotein that is implicated in myriad physiological and pathological conditions characterized... (Review)
Review
Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular glycoprotein that is implicated in myriad physiological and pathological conditions characterized by extensive remodeling and plasticity. The functions and disease association of SPARC in cancer is being increasingly appreciated as it plays multi-faceted contextual roles depending on the cancer type, cell of origin and the unique cancer milieu at both primary and metastatic sites. Herein we will review our current knowledge of the role of SPARC in the multistep cascades of urinary bladder carcinogenesis, progression and metastasis from preclinical models and clinical data and shine the light on its prognostic and therapeutic potentials.
Topics: Animals; Carcinogenesis; Disease Progression; Humans; Neoplasm Invasiveness; Osteonectin; Urinary Bladder Neoplasms; Urothelium
PubMed: 27564266
DOI: 10.18632/oncotarget.11590 -
International Journal of Molecular... Apr 2014Human stem cells are promising sources for bladder regeneration. Among several possible sources, pluripotent stem cells are the most fascinating because they can...
Human stem cells are promising sources for bladder regeneration. Among several possible sources, pluripotent stem cells are the most fascinating because they can differentiate into any cell type, and proliferate limitlessly in vitro. Here, we developed a protocol for differentiation of human pluripotent stem cells (hPSCs) into bladder urothelial cells (BUCs) under a chemically defined culture system. We first differentiated hPSCs into definitive endoderm (DE), and further specified DE cells into BUCs by treating retinoic acid under a keratinocyte-specific serum free medium. hPSC-derived DE cells showed significantly expressed DE-specific genes, but did not express mesodermal or ectodermal genes. After DE cells were specified into BUCs, they notably expressed urothelium-specific genes such as UPIb, UPII, UPIIIa, P63 and CK7. Immunocytochemistry showed that BUCs expressed UPII, CK8/18 and P63 as well as tight junction molecules, E-CADHERIN and ZO-1. Additionally, hPSCs-derived BUCs exhibited low permeability in a FITC-dextran permeability assay, indicating BUCs possessed the functional units of barrier on their surfaces. However, BUCs did not express the marker genes of other endodermal lineage cells (intestine and liver) as well as mesodermal or ectodermal lineage cells. In summary, we sequentially differentiated hPSCs into DE and BUCs in a serum- and feeder-free condition. Our differentiation protocol will be useful for producing cells for bladder regeneration and studying normal and pathological development of the human bladder urothelium in vitro.
Topics: Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Humans; Pluripotent Stem Cells; Serum; Urinary Bladder; Urothelium
PubMed: 24776760
DOI: 10.3390/ijms15057139 -
Asian Pacific Journal of Cancer... Apr 2022Evaluation of SOX-10 expression in malignant urothelial cells, comparing it with the phenotypically non neoplastic urothelium, and correlating it with the various...
OBJECTIVE
Evaluation of SOX-10 expression in malignant urothelial cells, comparing it with the phenotypically non neoplastic urothelium, and correlating it with the various clinicopathological variables, with a focus on the invasive pattern.
METHODS
Eighty paraffin blocks of urothelial carcinoma were stained by H&E. Histopathological features were evaluated and then immunostained with SOX-10 to evaluate its expression.
RESULTS
The evaluation of SOX-10 expression in urothelial carcinoma, revealed a high grade of SOX-10 expression in the malignant urothelium (4380 cases; 53.7%), while the adjacent the non neoplastic urothelium expressed high SOX-10 in (1242 case; 28.6%). Correlation of SOX-10 score with the various variables revealed a statistically significant correlation with the gross shape (P value=0.002), the tumor grade ((P value=0.009), the muscle invasion by the tumor ((P value=0.004), the tumor T stage, (P-value <0.001), N stage (P value=0.003), associated Schistoma hematobium infestation (P-value =0.016), and the presence of vascular tumor emboli (P-value =0.009). It was statistically insignificant with the gender, the anatomical site, and the perineural tumor invasion. Correlating the mean of SOX-10 score with some tumor features revealed a statistically significant correlation with the muscle invasion by the tumor, Tumor grade, T stage, and non neoplastic urothelium; P-value <0.001 each and N stage P value=0.006.
CONCLUSION
SOX-10 is overexpressed in urothelial carcinoma and it was also detected in a significant part of the surrounding non neoplastic urothelium, which may contribute to understanding its role in multistep urothelial carcinogenesis as transcription or tumor-promoting factor, thus it could be used in future trials for specific targeted therapy.
Topics: Carcinoma, Transitional Cell; Female; Humans; Hyperplasia; Male; Urinary Bladder Neoplasms; Urothelium
PubMed: 35485705
DOI: 10.31557/APJCP.2022.23.4.1425 -
International Braz J Urol : Official... 2020To show the main indications of retroperitoneoscopy (RP) for the treatment of urolithiasis. The use of RP approach has been limited, being narrow working space the major...
OBJECTIVE
To show the main indications of retroperitoneoscopy (RP) for the treatment of urolithiasis. The use of RP approach has been limited, being narrow working space the major issue to overcome (1), especially in non-expert hands. However, RP has the added advantages of no peritoneal contamination, a quick recovery of bowel function (2) and the possibility to use it in combination with other endourological techniques (3) and innovative technology.
MATERIALS AND METHODS
We performed a retrospective analysis of 22 patients treated by the retroperitoneoscopic approach due to urolithiasis disease between 2015-2017. Type of surgery, stone free rate (SFR), complications according to Clavien-Dindo classification and mean hospital stay were recorded. Radical and partial nephrectomy cases were excluded for the SFR calculation. Descriptive statistical analysis was done using SPSS v21.
RESULTS
Of the 22 patients treated by the retroperitoneoscopic approach, 9 underwent a ureterolithotomy, 4 underwent a nephrolithotomy, 8 were nephrectomies and 1 was a polar nephrectomy. In 3 cases we used the indocianine green fluorescence (ICG) to find avascular planes, reduce the bleeding, permitting enhanced visualization and reconstruction. In 3 cases an additional percutaneous approach was used, increasing the SFR chances. Eleven of thirteen (84.6%) patients were stone free following the procedure. Tree complications were recorded, two Clavien II and one Clavien III complications. Mean hospital stay was 4 days.
CONCLUSIONS
Retroperitoneoscopic approach is a good alternative for the treatment of large impacted ureteral stones, large pielic stones and for non-functional kidney removal due to stone disease. In expert hands, it can be safely used with a good SFR. The combination with ICG or other endourological techniques is feasible, allowing higher SFR.
Topics: Humans; Laparoscopy; Length of Stay; Retroperitoneal Space; Retrospective Studies; Urothelium
PubMed: 32374142
DOI: 10.1590/S1677-5538.IBJU.2019.0099 -
International Journal of Urology :... Jan 2013Traditionally, sensory signaling in the urinary bladder has been largely attributed to direct activation of bladder afferents. There is substantive evidence that sensory... (Review)
Review
Traditionally, sensory signaling in the urinary bladder has been largely attributed to direct activation of bladder afferents. There is substantive evidence that sensory systems can be influenced by non-neuronal cells, such as the urothelium, which are able to respond to various types of stimuli that can include physiological, psychological and disease-related factors. The corresponding release of chemical mediators (through activation of a number of receptors/ion channels) can initiate signaling mechanisms between and within urothelial cells, as well as other cell types within the bladder wall including bladder nerves. However, the mechanisms underlying how various cell types in the bladder wall respond to normal filling and emptying, and are challenged by a variety of stressors (physical and chemical) are still not well understood. Alterations or defects in signaling mechanisms are likely to contribute to the pathophysiology of bladder disease with symptoms including urinary urgency, increased voiding frequency and pain. This review will discuss some of the components involved in control of lower urinary tract function, with an emphasis on the sensor and transducer roles of the urothelium.
Topics: Afferent Pathways; Animals; Cell Communication; Humans; Urethra; Urinary Bladder; Urothelium
PubMed: 23088378
DOI: 10.1111/j.1442-2042.2012.03210.x -
Physiological Reports Jun 2022We previously identified a peptide derived from human fibroblast growth factor 7 (FGF7p) that blocks urothelial apoptosis similar to full-length FGF7, although effects...
We previously identified a peptide derived from human fibroblast growth factor 7 (FGF7p) that blocks urothelial apoptosis similar to full-length FGF7, although effects of FGF7p on urothelial repair are unknown. Also, while urothelial AKT activation downstream of FGF7p correlated with the anti-apoptotic effects, we have not directly interrogated the role of AKT in mediating the cytoprotection. Our goal was to assess effects of FGF7p on urothelial repair and the role of AKT signaling in mediating the cytoprotective effects of FGF7p. We performed hematoxylin and eosin (H&E), TUNEL, and/or immunofluorescence (IF) staining for various markers in FGF7p-treated mice 28 days after giving cyclophosphamide or after co-administering a systemic AKT antagonist with FGF7p 24 h after cyclophosphamide. Vehicle-treated and injured mice had hyperplastic urothelium, incomplete return of mature superficial cell markers, ongoing proliferation, and continued presence of basal progenitor markers 28 days after injury; conversely, FGF7p-treated mice had normal numbers of urothelial cell layers, nearly complete return of superficial cell markers, limited proliferation and fewer basal progenitor cells 28 days post-injury. Vehicle-treated mice also had ectopic lumenal basal progenitor cell markers, while FGF7p had none 28 days after cyclophosphamide. Co-administration of an AKT inhibitor largely abrogated FGF7p-driven AKT activation and cytoprotection in urothelium 24 h after injury. Thus, FGF7p drives faster and higher fidelity urothelial repair by limiting apoptotic injury via AKT signaling, similar to full-length FGF7. Finally, FGF7p is much less expensive to synthesize and has a longer shelf life and higher purity than FGF7.
Topics: Animals; Apoptosis; Cyclophosphamide; Cytoprotection; Mice; Proto-Oncogene Proteins c-akt; Urothelium
PubMed: 35748317
DOI: 10.14814/phy2.15358 -
Seminars in Immunopathology May 2018Intense research has focused on the involvement of the nervous system in regard to cellular mechanisms underlying neurogenic inflammation in the pelvic viscera. Evidence... (Review)
Review
Intense research has focused on the involvement of the nervous system in regard to cellular mechanisms underlying neurogenic inflammation in the pelvic viscera. Evidence supports the neural release of inflammatory factors, trophic factors, and neuropeptides in the initiation of inflammation. However, more recently, non-neuronal cells including epithelia, endothelial, mast cells, and paraneurons are likely important participants in nervous system functions. For example, the urinary bladder urothelial cells are emerging as key elements in the detection and transmission of both physiological and nociceptive stimuli in the lower urinary tract. There is mounting evidence that these cells are involved in sensory mechanisms and can release mediators. Further, localization of afferent nerves next to the urothelium suggests these cells may be targets for transmitters released from bladder nerves and that chemicals released by urothelial cells may alter afferent excitability. Modifications of this type of communication in a number of pathological conditions can result in altered release of epithelial-derived mediators, which can activate local sensory nerves. Taken together, these and other findings highlighted in this review suggest that neurogenic inflammation involves complex anatomical and physiological interactions among a number of cell types in the bladder wall. The specific factors and pathways that mediate inflammatory responses in both acute and chronic conditions are not well understood and need to be further examined. Elucidation of mechanisms impacting on these pathways may provide insights into the pathology of various types of disorders involving the pelvic viscera.
Topics: Animals; Humans; Neurogenic Inflammation; Urinary Bladder; Urothelium
PubMed: 29582112
DOI: 10.1007/s00281-018-0674-0 -
Neurourology and Urodynamics Feb 2016To present a synopsis of the presentations and discussions from Think Tank I, "Implications for afferent-urothelial bidirectional communication" of the 2014... (Review)
Review
AIMS
To present a synopsis of the presentations and discussions from Think Tank I, "Implications for afferent-urothelial bidirectional communication" of the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK.
METHODS
The participants presented what is new, currently understood or still unknown on afferent-urothelial signaling mechanisms. New avenues of research and experimental methodologies that are or could be employed were presented and discussed.
RESULTS
It is clear that afferent-urothelial interactions are integral to the regulation of normal bladder function and that its disruption can have detrimental consequences. The urothelium is capable of releasing numerous signaling factors that can affect sensory neurons innervating the suburothelium. However, the understanding of how factors released from urothelial cells and afferent nerve terminals regulate one another is incomplete. Utilization of techniques such as viruses that genetically encode Ca(2+) sensors, based on calmodulin and green fluorescent protein, has helped to address the cellular mechanisms involved. Additionally, the epithelial-neuronal interactions in the urethra may also play a significant role in lower urinary tract regulation and merit further investigation.
CONCLUSION
The signaling capabilities of the urothelium and afferent nerves are well documented, yet how these signals are integrated to regulate bladder function is unclear. There is unquestionably a need for expanded methodologies to further our understanding of lower urinary tract sensory mechanisms and their contribution to various pathologies.
Topics: Animals; Congresses as Topic; Epithelial Cells; Humans; Neurons, Afferent; Neurons, Efferent; Synaptic Transmission; Urinary Bladder; Urothelium
PubMed: 26872567
DOI: 10.1002/nau.22839