Endocytotic activity of bladder superficial urothelial cells is inversely related to their differentiation stage

Kreft, Mateja Erdani; Romih, Rok; Kreft, Marko; Jezernik, Kristijan

doi:10.1016/j.diff.2008.09.011

Cited by 48 publications

(64 citation statements)

References 40 publications

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“…BBN is widely used in the urothelial carcinogenesis model systems and prevents urothelial cells reaching their terminal differentiation. 45,46 A consequence of low cellular differentiation is leaky epithelium, 38,47 which was also observed in our study. The AuNPs were commonly found in the partially differentiated cells of neoplastically transformed urothelium.…”

Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 96%

“…38 Despite the high concentration of nanoparticles in the bladder lumen, only one quarter of cells contained a few labeled endosomes, which shows extremely low dynamics of endocytosis compared to other cell types. 38 Nanoparticles were not found in the FVs, demonstrating that FVs are not involved in the removal of urothelial plaques from the apical plasma membrane. Limited internalization of nanoparticles into terminally differentiated superficial urothelial cells hence supports the idea that internalization of urine and its constituents is minimized, which contributes to the barrier function of the urothelium.…”

Section: Discussionmentioning

confidence: 96%

“…Since there are contradicting results regarding endocytosis in urothelial cells, 3,19,37,38 we used the AuNPs to follow internalization into superficial urothelial cells of normal and neoplastic urothelium.…”

Section: Discussionmentioning

confidence: 99%

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Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo

Hudoklin¹,

Zupančič²,

Makovec³

et al. 2013

IJN

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Background: Urothelial bladder is the reservoir of urine and the urothelium minimizes the exchange of urine constituents with this tissue. Our aim was to test 1.9 nm biocompatible gold nanoparticles as a novel marker of internalization into the urothelial cells under physiological conditions in vivo. Methods: We compared normal and neoplastic mice urothelium. Neoplastic lesions were induced by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water for 10 weeks. Nanoparticles, intravenously injected into normal and BBN-treated mice, were filtered through the kidneys and became constituents of the urine within 90 minutes after injection. Results: Gold nanoparticles were densely accumulated in the urine, while their internalization into urothelial cells depended on the cell differentiation stage. In the terminally differentiated superficial urothelial cells of normal animals, nanoparticles were occasionally found in the endosomes, but not in the fusiform vesicles. Regions of exfoliated cells were occasionally found in the normal urothelium. Superficial urothelial cells located next to exfoliated regions contained gold nanoparticles in the endosomes and in the cytosol beneath the apical plasma membrane. The urothelium of BBN-treated animals developed flat hyperplasia with moderate dysplasia. The superficial cells of BBN-treated animals were partially differentiated as demonstrated by the lack of fusiform vesicles. These cells contained the gold nanoparticles distributed in the endosomes and throughout their cytosol. Conclusion: Gold nanoparticles are a valuable marker to study urine internalization into urothelial cells in vivo. Moreover, they can be used as a sensitive marker of differentiation and functionality of urothelial cells.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo

Hudoklin¹,

Zupančič²,

Makovec³

et al. 2013

IJN

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“…Chemical agents are commonly used to induce IC in animal models with the intention to directly degrade the GAG layer and alter intercellular tight junctions, thus reducing barrier effectiveness (19). Cyclophosphamide (CyP) is commonly used for the treatment of cancers as well as for various autoimmune diseases, however, many patients manifested an unpleasant IC like symptoms as side effect afterward the therapy (20).…”

Section: Induced Ic Animal Models With Effects On Gags Depletion and mentioning

confidence: 99%

Reviewing Interstitial Cystitis Models and Treatments: A Focus on the Urothelium

F¹

2017

Razavi Int J Med

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Context: Interstitial cystitis is a multifactorial chronic and debilitating disease which is commonly associated with pain localized in the bladder region, increased urinary frequency, urgency and nocturia. Due to the high prevalence of pain in the population affected more recently the condition is often referred to as interstitial cystitis / bladder pain syndrome (IC/BPS). Evidence Acquisition: Although IC presents with many different symptoms, researchers have formulated three different theories, which are not mutually exclusive, to explain IC pathology: the first is related to the alteration of the proteoglycan and protein junction composition, structure and presence in the urothelium. The second is an immune induced IC resulting from an increased number of activated mast cells in the bladder internal layers, such as detrusor muscle (DM), and mucosa/submucosa. The third type, which is closely related to the second one, is due to a sensory nerve sensitization as an effect of neurotrophic factors molecule release. Results: Previous classification has been mirrored in the development of various in vitro and in vivo disease models created to mimic IC, as well as in the available therapies used to treat the condition to date. Conclusions: This review will summarize the most recent advances in the field, related to the different causative factors contributing to the development of the condition, the in vivo models used as well as the evidence they provide in advancing our knowledge and their limitations. The focus will be on works reporting on IC in the domain related to alterations in proteoglycans and cellular junction, specifically their composition, structure and appearance in the urothelium, and also discuss present and future therapies. Conclusions: This review will summarize the most recent advances in the field, related to the different causative factors contributing to the development of the condition, the in vivo models used as well as the evidence they provide in advancing our knowledge and their limitations. The focus will be on works reporting on IC in the domain related to alterations in proteoglycans and cellular junction, specifically their composition, structure and appearance in the urothelium, and also discuss present and future therapies.

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Co‐culturing porcine normal urothelial cells, urinary bladder fibroblasts and smooth muscle cells for tissue engineering research

Zupančič

Poljšak

Kreft

2017

Cell Biology International

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New strategies for culturing and co-culturing of the main types of urinary bladder cells are essential for successful establishment of biomimetic in vitro models, which could be applied for research into, and management of, diverse urological disorders. Porcine normal urothelial cells are available in nearly unlimited amounts and have many properties equivalent to human urothelial cells. In the present study, we established normal differentiated porcine urothelial cells in co-cultures with porcine urinary bladder normal fibroblasts and/or smooth muscle cells. The optimal culture medium for establishment of differentiated urothelial cells, demonstrated by positive immunofluorescence of uroplakins, cytokeratins (CK 7, CK 20), zonula occludens 1 (ZO-1), claudin 4, claudin 8, and E-cadherin, was the medium composed of equal parts of Advanced Dulbecco's modified Eagle's medium (A-DMEM) and MCDB 153 medium with physiological calcium concentration of 2.5 mM and without fetal bovine serum, named UroM (+Ca - S). This medium was also proven to be suitable for culturing of bladder fibroblasts and smooth muscle cells and co-culturing of urothelial cells with these mesenchymal cells. Urothelial cell differentiation was optimal in UroM (+Ca - S) medium in all co-culture conditions and when compared to all conditioned-media combinations. To summarize, these strategies for culturing and co-culturing of urinary bladder urothelial cells with mesenchymal cells could be used as new in vitro models for future basic and applicable research of the urinary bladder and thus potentially also for translational tissue engineering studies.

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Endocytotic activity of bladder superficial urothelial cells is inversely related to their differentiation stage

Cited by 48 publications

References 40 publications

Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo

Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo

Reviewing Interstitial Cystitis Models and Treatments: A Focus on the Urothelium

Co‐culturing porcine normal urothelial cells, urinary bladder fibroblasts and smooth muscle cells for tissue engineering research

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