Proliferation of Submesothelial Mesenchymal Cells during Early Phase of Serosal Thickening in the Rabbit Bladder Is Accompanied by Transient Keratin 18 Expression

Pampinella, Francesca; Roelofs, Marleen; Castellucci, Enrico; Chiavegato, Angela; Guidolin, Diego; Passerini-Glazel, Giacomo; Pagano, F.; Sartore, Saverio

doi:10.1006/excr.1996.0088

Cited by 15 publications

(12 citation statements)

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“…The increased bladder mass of the PACAP −/− mice was consistent with cystometry and urine spot data that demonstrated increased VV and fewer but significantly larger urine spots. PACAP −/− mice also exhibit increased lamina propria thickness as previously shown in animal models of outlet obstruction 23. Reasons underlying increased lamina propria thickness in PACAP −/− mice may include tissue remodeling of the afferent and efferent nerves 24 present in the suburothelial plexus and detrusor 25, myofibroblasts and/or vasculature 26 as previously described in animal models of outlet obstruction and potentially influenced by changes in urinary bladder NGF content 24, 27.…”

Section: Discussionsupporting

confidence: 55%

Bladder Dysfunction and Altered Somatic Sensitivity in PACAP ^−/− Mice

May

Vizzard

2010

Journal of Urology

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Purpose Pituitary adenylate cyclase activating polypeptide (PACAP) and receptors are expressed in micturition pathways. Studies demonstrated roles for PACAP in detrusor smooth muscle contraction, facilitating ATP release from urothelium and PACAP antagonism reduced cyclophosphamide-induced bladder hyperreflexia. Materials and Methods PACAP contributions to micturition and somatic sensation were studied in PACAP knockout (PACAP−/−), littermate heterozygote (PACAP+/−) and wildtype (WT) mice using conscious cystometry with continuous intravesical saline or acetic acid (AA; 0.5%) instillation, urination patterns, somatic sensitivity testing of hindpaw and pelvic region with calibrated von Frey filaments and morphological assessments of urinary bladder. Results PACAP−/− mice exhibit increased bladder mass with fewer but larger urine spots. In PACAP−/− mice, the lamina propria and detrusor smooth muscle are significantly thicker whereas the urothelium is unchanged. PACAP−/− mice exhibit increased bladder capacity, void volume (VV) and longer intercontraction interval (ICI) with significantly increased detrusor contraction duration and large residual volume. WT mice respond to AA (0.5%) with a reduction in VV and a decreased ICI whereas PACAP+/− and PACAP−/− mice do not respond. PACAP−/− mice are less responsive to somatic stimulation. PACAP+/− also exhibit bladder dysfunction and somatic and visceral sensory abnormalities but to a lesser degree. Conclusions PACAP gene disruption contributes to changes in bladder morphology, bladder function and somatic and visceral hypoalgesia.

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Section: Discussionsupporting

confidence: 55%

Bladder Dysfunction and Altered Somatic Sensitivity in PACAP ^−/− Mice

May

Vizzard

2010

Journal of Urology

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“…(3) Individual progenitor cells may be preexisting within all layers of the bladder wall but enter the cell cycle at different time points after STC injury. Consistent with this hypothesis, enquires into the existence of a bladder progenitor cell using BrdU-labeled rabbit models suggest that subepithelial, mesenchymal cells can rapidly proliferate, differentiate and integrate into smooth muscle bundles in response to mechanical stress (outlet obstruction) [31] and cryogenic injury [27]. However, investigating the presence of proliferating cells co-labeled with various stem cell markers (Lgr5, CD-34, SSEA-1, c-kit) has proved challenging [50].…”

Section: Discussionmentioning

confidence: 83%

“…The goal of this investigation was to gain additional mechanistic insight into the spatiotemporal characteristics of this cellular response during the early stages (first week) of regeneration. Specifically, we evaluated the proliferative cellular response during the first week following STC using fluorescent BrdU cell labeling, a label-retaining technique that has been utilized to investigate a variety of stem/progenitor cell niches including liver, kidney, intestine, and previous bladder injury models [26], [27], [28], [29], [30], [31], [32], [33]…”

Section: Discussionmentioning

confidence: 99%

“…A literature review reveals several studies that have characterized increased urothelial proliferation in response to injury (e.g., bacteria, cryogenic ablation, or outlet obstruction) [27], [31], [34]. These investigations have highlighted a variety of transcriptional factors that may play an important role in the reconstitution of bladder wall cells, including evolutionarily conserved participants in hedgehog signaling, such as sonic hedgehog (Shh), Gli-1, and bone morphogenetic protein-4 (BMP-4) [31], [33], [34].…”

Section: Discussionmentioning

confidence: 99%

“…These investigations have highlighted a variety of transcriptional factors that may play an important role in the reconstitution of bladder wall cells, including evolutionarily conserved participants in hedgehog signaling, such as sonic hedgehog (Shh), Gli-1, and bone morphogenetic protein-4 (BMP-4) [31], [33], [34]. Additionally, recent studies have attempted to identify bladder-specific progenitor cells that may, at least in part, participate in the observed functional recovery after injury [35], [36]…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the Early Proliferative Response of the Rodent Bladder to Subtotal Cystectomy: A Unique Model of Mammalian Organ Regeneration

et al. 2012

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Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder) elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU). Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP), muscularis propria (MP) and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA), to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh), Gli-1 and bone morphogenic factor-4 (BMP-4) were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends previous observations and further establishes the rodent bladder as an excellent model for studying novel aspects of mammalian organ regeneration.

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Epididymal Growth and Differentiation Are Altered in Human Cryptorchidism

de MIGUEL,

MARIÑO,

GONZALEZ‐PERAMATO

et al. 2001

Journal of Andrology

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Despite the knowledge and histological classification of testicular lesions, epididymal lesions associated with cryptorchidism are not well defined and only macroscopic alterations have been reported. We have evaluated the alterations in the growth of both the epithelium and muscular wall of efferent ducts and epididymis in human patients with cryptorchidism from infancy to adulthood. In addition, by cytokeratin immunostaining we have also evaluated the stage of differentiation of each segment along the human postnatal life in these patients. A decrease is shown in the size of efferent and epididymal ducts in cryptorchid children compared with normal, age‐matched controls. The height of the epithelium, muscular wall, and lumen of the cryptorchid epididymis were reduced at every age studied. This decrease in all regions was seen even in the testicular quiescent period (1 to 4 years of age). In addition, the cryptorchid epididymis grows more slowly during the transition to the pubertal period. The smaller size of the cryptorchid epididymis in pubertal and adult men compared with that of normal men is due primarily to underdevelopment of the muscular wall and a reduction in epithelial height. The pattern of growth of cryptorchid efferent ducts and ductus epididymides parallels that in normal men, except that development of the lumen and muscular layer in the cauda epididymis region are delayed. Epithelial differentiation, monitored by cytokeratin expression, is minimal in efferent ducts and throughout the epididymis of the cryptorchid male, and this is already seen in children. In conclusion, our immunohistochemical and morphometric results show a reduced development of the human cryptorchid epididymis that is already evident in childhood. They indicate that cryptorchidism is a primary congenital illness of the testis and spermatic ducts, with evident lesions from the first years of life, and suggest that surgical descent would probably not be able to completely reverse these alterations.

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Proliferation of Submesothelial Mesenchymal Cells during Early Phase of Serosal Thickening in the Rabbit Bladder Is Accompanied by Transient Keratin 18 Expression

Cited by 15 publications

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Bladder Dysfunction and Altered Somatic Sensitivity in PACAP ^−/− Mice

Bladder Dysfunction and Altered Somatic Sensitivity in PACAP ^−/− Mice

Characterization of the Early Proliferative Response of the Rodent Bladder to Subtotal Cystectomy: A Unique Model of Mammalian Organ Regeneration

Epididymal Growth and Differentiation Are Altered in Human Cryptorchidism

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Proliferation of Submesothelial Mesenchymal Cells during Early Phase of Serosal Thickening in the Rabbit Bladder Is Accompanied by Transient Keratin 18 Expression

Cited by 15 publications

References 0 publications

Bladder Dysfunction and Altered Somatic Sensitivity in PACAP −/− Mice

Bladder Dysfunction and Altered Somatic Sensitivity in PACAP −/− Mice

Characterization of the Early Proliferative Response of the Rodent Bladder to Subtotal Cystectomy: A Unique Model of Mammalian Organ Regeneration

Epididymal Growth and Differentiation Are Altered in Human Cryptorchidism

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Bladder Dysfunction and Altered Somatic Sensitivity in PACAP ^−/− Mice

Bladder Dysfunction and Altered Somatic Sensitivity in PACAP ^−/− Mice