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Comprehensive transcriptome profiling of urothelial cells following TNFα stimulation in an in vitro interstitial cystitis/bladder pain syndrome model
ID Kuret, Tadeja (Avtor), ID Peskar, Dominika (Avtor), ID Erdani-Kreft, Mateja (Avtor), ID Erman, Andreja (Avtor), ID Veranič, Peter (Avtor)

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Izvleček
Urothelial cells of the urinary bladder play a critical role in the development and progression of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic and debilitating inflammatory disease. Given the lack of data on the exact phenotype and function of urothelial cells in an inflammatory setting (as in IC/BPS), we performed the first in-depth characterization of these cells using RNA sequencing, qPCR, ELISA, Western blot, and immunofluorescence. After TNFα stimulation, urothelial cells in the in vitro model of IC/BPS showed marked upregulation of several proinflammatory mediators, such as SAA, C3, IFNGR1, IL1α, IL1β, IL8, IL23A, IL32, CXCL1, CXCL5, CXCL10, CXCL11, TNFAIPR, TNFRSF1B, and BIRC3, involved in processes and pathways of innate immunity, including granulocyte migration and chemotaxis, inflammatory response, and complement activation, as well as TLR-, NOD-like receptor- and NFkB-signaling pathways, suggesting their active role in shaping the local immune response of the bladder. Our study demonstrates that the TNFα-stimulated urothelial cells recapitulate key observations found in the bladders of patients with IC/BPS, underpinning their utility as a suitable in vitro model for understanding IC/BPS mechanisms and confirming the role of TNFα signaling as an important component of the associated pathology. The present study also identifies novel upregulated gene targets of TNFα in urothelial cells, including genes encoding the acute phase protein SAA, complement component C3, and the cytokine receptor IFNGR1, which could be exploited as therapeutic targets of IC/BPS. Altogether, our study provides a reference database of the phenotype of urothelial cells in an inflammatory environment that will not only increase our knowledge of their role in IC/BPS, but also advance our understanding of how urothelial cells shape tissue immunity in the bladder.

Jezik:Angleški jezik
Ključne besede:interstitial cystitis, bladder pain syndrome, urothelial cells, inflammation, RNA sequencing, transcriptomics, proinflammatory cytokines
Vrsta gradiva:Članek v reviji
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:MF - Medicinska fakulteta
Status publikacije:Objavljeno
Različica publikacije:Objavljena publikacija
Leto izida:2022
Št. strani:16 str.
Številčenje:Vol. 13, art. 960667
PID:20.500.12556/RUL-145374 Povezava se odpre v novem oknu
UDK:616.6
ISSN pri članku:1664-3224
DOI:10.3389/fimmu.2022.960667 Povezava se odpre v novem oknu
COBISS.SI-ID:118210307 Povezava se odpre v novem oknu
Datum objave v RUL:19.04.2023
Število ogledov:566
Število prenosov:89
Metapodatki:XML DC-XML DC-RDF
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Gradivo je del revije

Naslov:Frontiers in immunology
Skrajšan naslov:Front. immunol.
Založnik:Frontiers Research Foundation
ISSN:1664-3224
COBISS.SI-ID:30774233 Povezava se odpre v novem oknu

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:intersticijski cistitis, sindrom bolečine v mehurju, urotelijske celice

Projekti

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:J3-2521
Naslov:Vnetni proces pri intersticijskem cistitisu in ovrednotenje delovanja agonistov kanabinoidnih receptorjev sečnega mehurja – od celic do pacienta

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:J7-2594
Naslov:Uporaba amnijske membrane za inovativno multimodalno zdravljenje bakterijskega cistitisa in raka sečnega mehurja: učinek njene protimikrobne, imunomodulatorne in protirakave aktivnosti

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:P3-0108
Naslov:Diferenciacija urotelijskih celic

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:I0-0022
Naslov:Mreža raziskovalnih infrastrukturnih centrov Univerze v Ljubljani (MRIC UL)

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