Epithelial Dysfunction in Nonbacterial Cystitis (Interstitial Cystitis)

Parsons, C. Lowell; Lilly, Joel D.; Stein, Paul C.

doi:10.1016/s0022-5347(17)38437-9

Cited by 367 publications

(163 citation statements)

References 31 publications

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“…We based our project on the Parsons hypothesis of IC pathogenesis, where GAG layer protects the epithelium against the urine (13). Because ER␤ has been shown to be necessary for terminal differentiation in the prostate, mammary gland and colon, we hypothesized that, in the absence of ER␤ signaling, bladder urothelium could have an altered differentiation, which could cause alterations in GAG production and subsequently failure of the bladder wall to protect against the hostile environment of urine.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor β-deficient female mice develop a bladder phenotype resembling human interstitial cystitis

Imamov

Yakimchuk

Morani

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Interstitial cystitis/painful bladder syndrome is a disease seen mostly in women, and symptoms tend to be worse premenopausally or during ovulation. The four cardinal symptoms of interstitial cystitis/painful bladder syndrome are bladder pain, urgency, frequency, and nocturia. Estrogen has been implicated in the etiology of this disease, but the role of the two estrogen receptors (ER), ER␣ and ER␤, has not been investigated. We found that, in the bladders of WT mice, ER␤ is expressed in the basal cell layer of the urothelium. Bladders of male ER␤ ؊/؊ mice were intact and morphologically indistinguishable from those of their WT littermates. However, in female ER␤ ؊/؊ mice, there was ulceration and atrophy of bladder urothelium concomitant with infiltration of ␥␦ T cells concentrated in the areas of atrophy and shedding of urothelium. The data support the idea that activated ␥␦ T cells are causing the damage to the urothelium. The hyperactivity of T cells may be because of an imbalance between ER␣ and ER␤ signaling in female ER␤ ؊/؊ mice. Our data suggest that reduced ER␤ signaling might have a role in the pathogenesis of interstitial cystitis, and ER␤ could be a candidate for a target of medical therapy.␥␦ T cells ͉ urothelium ͉ painful bladder syndrome T he etiology of interstitial cystitis (IC) is unknown, and available treatment options are limited and mostly palliative. There is a clear role for the immune system in this disease: increased numbers of T lymphocytes, particularly ␥␦ T cells, abnormal urothelial HLA, and overexpression of HLA class II (1) in the urothelium and lamina propria in patients with IC strongly suggest a role for autoimmunity in development of IC (2). Because IC is almost exclusively a disease of young women, and symptoms tend to worsen premenopausally or during ovulation, the role of estrogen receptors (ERs) is likely to be important.The bladder is one of those tissues that were long thought to be nonestrogen-responsive on the basis of the lack of ER␣ expression. The discovery of the second ER, ER␤, provided an explanation for the effects of estrogen in several ER␣-negative tissues such as the prostate, intestine, and lung, where ER␤ serves as a modulator of terminal differentiation of epithelium (3-7). ER␤ and ER␣ knockout mice (ER␤ Ϫ/Ϫ and ER␣ Ϫ/Ϫ ) have been invaluable in analyzing and dissecting the functions of ER␤ and ER␣ (8, 9).The predominant ER in the bladder is ER␤, with very little ER␣ expression (10, 11). Reduced ER␤ expression levels have been reported in the bladders of rats with chemically induced cystitis (12). In the present study, with the use of ER␤ Ϫ/Ϫ mice, we have investigated the role of ER␤ in the bladder urothelium. We report that, in female ER␤ Ϫ/Ϫ but not in ER␣ Ϫ/Ϫ mice, there is autoimmune destruction of urothelium resembling IC. ResultsImmunohistochemical staining of WT mouse bladder sections showed that ER␤ is expressed in bladder urothelium and localized in the basal cell layer (Fig. 1). In the bladders of female ER␤ Ϫ/Ϫ mice, there were specific morphol...

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Section: Discussionmentioning

confidence: 99%

Estrogen receptor β-deficient female mice develop a bladder phenotype resembling human interstitial cystitis

Imamov

Yakimchuk

Morani

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Плоскоклеточную метаплазию можно рассматривать как вариант компенсаторно-при-способительной реакции. Однако отсутствие при плоскоклеточной метаплазии плотных контактов между смежными поверхностными клетками и люминальной асимметричной еди-ной мембраной и вследствие этого нарушение проницаемости эпителиального барьера ука-зывают на неполноценность такой компенса-ции [13].…”

Section: результаты и обсуждениеunclassified

Disorders of bladder microcirculation and morphologic changes in women with leukoplakia of the bladder

Al-Shukri

Kuzmin

Slesarevskaya

et al. 2016

UroVed

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“…The patho-etiology of IC/BPS has remained enigmatic, although several theories have been proposed. [4][5][6][7][8][9][10] The demonstration from several clinicians 2,[11][12][13][14][15] of an association between childhood bladder and bowel dysfunction (BBD; previously called dysfunctional elimination syndrome or DES) and the development of lower urinary tract symptoms (LUTS) in adulthood supports a longitudinal process in some patients with overactive bladder (OAB). The strong prevalence of irritable bowel syndrome (IBS) in patients with IC/BPS has been identified by many authors.…”

Section: Introductionmentioning

confidence: 99%

Childhood bladder and bowel dysfunction predicts irritable bowel syndrome phenotype in adult interstitial cystitis/bladder pain syndrome patients

d’Oiron

Kogan

Tolls

et al. 2017

CUAJ

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Introduction: Many clinicians have suggested that a history of bladder and bowel dysfunction (BBD) in childhood predisposes to the development of interstitial cystitis/bladder pain syndrome (IC/BPS) or irritable bowel syndrome (IBS) in adulthood. We hypothesized that BBD symptoms in childhood would predict the IBS-associated phenotype in adult IC/BPS patients. Methods: Consecutive female patients (n=190) with a diagnosis of IC/BPS were administered a modified form of a clinical BBD questionnaire (BBDQ) to capture childhood BBD-like symptoms, as well as Interstitial Cystitis Symptoms Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/ Frequency (PUF) questionnaires and UPOINT categorization. Patients were stratified to IBS-positive or IBS-negative according to clinical assessment of IBS-like symptoms. Results: The 127 patients (67%) identified with IBS-like symptoms recalled significantly higher BBDQ scores than the 63 patients (33%) who were IBS-negative (2.8 vs. 2.3; p=0.05). The IBS-positive patients also reported a higher number of UPOINT domains than their non-IBS counterparts (3.8 vs. 2.9; p=0.0001), while their PUF total scores were significantly higher (13.6 vs. 12.3; p=0.04). IBSpositive patients more often recalled that in childhood they did not have a daily bowel movement (BM) (p=0.04) and had "to push for a BM" (p=0.009). In childhood, they "urinated only once or twice per day" (p=0.03) and recalled "painful urination" more than those without IBS (p=0.03). There were no significant differences between the groups in answers to the other five questions of the BBDQ. Conclusions: Our symptom recollection survey was able to predict the IBS phenotype of IC/BPS based on a childhood BBDQ. Further prospective studies are needed to further evaluate these novel findings.

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Epithelial Dysfunction in Nonbacterial Cystitis (Interstitial Cystitis)

Cited by 367 publications

References 31 publications

Estrogen receptor β-deficient female mice develop a bladder phenotype resembling human interstitial cystitis

Estrogen receptor β-deficient female mice develop a bladder phenotype resembling human interstitial cystitis

Disorders of bladder microcirculation and morphologic changes in women with leukoplakia of the bladder

Childhood bladder and bowel dysfunction predicts irritable bowel syndrome phenotype in adult interstitial cystitis/bladder pain syndrome patients

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