Moderate stress protects female mice against bacterial infection of the bladder by eliciting uroepithelial shedding

Dalal, Eilata; Medalia, Ora; Harari, Orna; Aronson, Moshe

doi:10.1128/iai.62.12.5505-5510.1994

Cited by 32 publications

(9 citation statements)

References 8 publications

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“…faecalis harbored within the urothelial cells of chronic UTI patients 55 . This previous report also slowed sloughing of umbrella cells from the epithelial lining into the urine, which is known in both mice and humans to be a common response to infection 67 – 71 . These findings were echoed in our urothelial organoid, where E .…”

Section: Discussionmentioning

confidence: 52%

A urine-dependent human urothelial organoid offers a potential alternative to rodent models of infection

Horsley

Dharmasena

Malone‐Lee

et al. 2018

Sci Rep

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Murine models describe a defined host/pathogen interaction for urinary tract infection, but human cell studies are scant. Although recent human urothelial organoid models are promising, none demonstrate long-term tolerance to urine, the natural substrate of the tissue and of the uropathogens that live there. We developed a novel human organoid from progenitor cells which demonstrates key structural hallmarks and biomarkers of the urothelium. After three weeks of transwell culture with 100% urine at the apical interface, the organoid stratified into multiple layers. The apical surface differentiated into enlarged and flattened umbrella-like cells bearing characteristic tight junctions, structures resembling asymmetric unit membrane plaques, and a glycosaminoglycan layer. The apical cells also expressed cytokeratin-20, a spatial feature of the mammalian urothelium. Urine itself was necessary for full development, and undifferentiated cells were urine-tolerant despite the lack of membrane plaques and a glycosaminoglycan layer. Infection with Enterococcus faecalis revealed the expected invasive outcome, including urothelial sloughing and the formation of intracellular colonies similar to those previously observed in patient cells. This new biomimetic model could help illuminate invasive behaviours of uropathogens, and serve as a reproducible test bed for disease formation, treatment and resolution in patients.

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Section: Discussionmentioning

confidence: 52%

A urine-dependent human urothelial organoid offers a potential alternative to rodent models of infection

Horsley

Dharmasena

Malone‐Lee

et al. 2018

Sci Rep

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“…Several authors have demonstrated rapid desquamation of urothelial cells following induction of a variety of stress syndromes (Dalal et al. ; Jezernik et al. ; Veramic and Jezernik ; Apodaca et al.…”

Section: Discussionmentioning

confidence: 99%

“…noted patchy areas of urothelial desquamation (single or multiple umbrella cells) and dilatation of extra cellular spaces (if urine was in the bladder) following 96 h constant environmental illumination, or single‐intraperitoneal injection of stress hormones (norepinephrine and hydrocortisone) in mice (Dalal et al. ; Jezernik et al. ; Veramic and Jezernik ).…”

Section: Discussionmentioning

confidence: 99%

The urothelium of a hibernator: the American black bear

et al. 2015

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The American black bear undergoes a 3–5 month winter hibernation during which time bears do not eat, drink, defecate, or urinate. During hibernation renal function (GFR) is 16–50% of normal but urine is reabsorbed across the urinary bladder (UB) urothelium thus enabling metabolic recycling of all urinary constituents. To elucidate the mechanism(s) whereby urine is reabsorbed, we examined the UBs of five nonhibernating wild bears using light, electron (EM), and confocal immunofluorescent (IF) microscopy–concentrating on two components of the urothelial permeability barrier – the umbrella cell apical membranes and tight junctions (TJ). Bear UB has the same tissue layers (serosa, muscularis, lamina propria, urothelia) and its urothelia has the same cell layers (basal, intermediate, umbrella cells) as other mammalians. By EM, the bear apical membrane demonstrated a typical mammalian scalloped appearance with hinge and plaque regions – the latter containing an asymmetric trilaminar membrane and, on IF, uroplakins Ia, IIIa, and IIIb. The umbrella cell TJs appeared similar to those in other mammals and also contained TJ proteins occludin and claudin - 4, and not claudin –2. Thus, we were unable to demonstrate urothelial apical membrane or TJ differences between active black bears and other mammals. Expression and localization of UT-B, AQP-1 and -3, and Na+, K+-ATPase on bear urothelial membranes was similar to that of other mammals. Similar studies of urothelia of hibernating bears, including evaluation of the apical membrane lipid bilayer and GAGs layer are warranted to elucidate the mechanism(s) whereby hibernating bears reabsorb their daily urine output and thus ensure successful hibernation.

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“…Acute and chronic stress due to abuse can alter these circuits, their neurochemical components, and bladder function [24,25]. In animal models stress changes bladder histology en physiology [26][27][28][29][30]. Link et al also mentions a role for corticotrophin-releasing factor (CRF), a primary neurotransmitter expressed by neurons within the central stress network [3].…”

Section: Discussionmentioning

confidence: 99%

Urological Complaints and Sexual Abuse: A Case Control Study Identifying Multiple Urological Complaints in Relation to Sexual Abuse History

Beck¹,

Nicolai²,

Putter³

et al. 2013

ASM

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Introduction: The relationship between sexual abuse and urinary tract symptoms has been described for urgency, frequency and nocturia. Aims: To investigate if other urological complaints in females, like urinary tract infections, incontinence, voiding complaints and lower abdominal pain are also correlated with a history of sexual abuse (SA) and to measure the prevalence of sexual abuse in our urological patient population, using a clinical case control study. Methods: 1383 female patients of 18-year-old or older visiting our outpatient urological university clinic were asked to fill out a questionnaire evaluating referral indications and urological complaints. The questionnaire consisted out of two parts. The first part was designed characteristics and medical history. The second part included referral indications, the urological complaints and a possible history of SA. The sample was divided into two groups: those with and those without a history of SA. The Outcome Measures: 1) The comparison of the frequency of voiding complaints, urinary tract infections (UTI's), lower abdominal pain, hematuria and incontinence in respondents with and without SA; 2) The prevalence of SA in female patients presenting at our university urological outpatient clinic; 3) The number of urological symptoms presented at the time of referral by respondents with a history of SA compared the non-abused. Results: 436/1383 (32%) patients were willing to participate. 304 (70%) questionnaires were properly filled in. The reported prevalence of sexual abuse was 17% (51/304). More than half of the females with a history SA presented with voiding complaints (32/51 p = 0.18), incontinence (31/51 p = 0.10) and urinary tract infections (27/51 p = 0.22). However, comparing the data of respondents without SA we found no significant differences with regards specific complaints. Patients with SA report more symptoms than those without (Armitage's trend test 0.14 (p = 0.004) for 4 complaints or more). Conclusions: No significant correlation between SA and voiding complaints, incontinence nor lower abdominal pain was found. The prevalence rate of SA in female patients visiting our university urological outpatient clinic was 17%. These abused females mentioned more synchronous complaints as reason for referral at their first visit than the non-abused.

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Moderate stress protects female mice against bacterial infection of the bladder by eliciting uroepithelial shedding

Cited by 32 publications

References 8 publications

A urine-dependent human urothelial organoid offers a potential alternative to rodent models of infection

A urine-dependent human urothelial organoid offers a potential alternative to rodent models of infection

The urothelium of a hibernator: the American black bear

Urological Complaints and Sexual Abuse: A Case Control Study Identifying Multiple Urological Complaints in Relation to Sexual Abuse History

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