| Autor: |
Alina Reicherz, Felipe Eltit, Kymora Scotland, Khaled Almutairi, Robert Bell, Bita Mojtahedzadeh, Michael Cox, Ben Chew, Dirk Lange |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Scientific Reports, Vol 13, Iss 1, Pp 1-14 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-023-31885-1 |
| Popis: |
Abstract To explore the pathways and mechanisms driving inflammation and fibrosis in stented ureters. In total, six healthy female pigs underwent cystoscopic unilateral ureteral stent insertion (6 Fr). After 14 days indwelling time, ureteral tissue was harvested in three pigs, while the remaining three pigs had their stents removed, and were recovered for 7 days. Three separate pigs served as controls. Tissue from stented and contralateral ureters was analysed histologically to evaluate tissue remodelling and classify the degree of inflammation and fibrosis, while genome, proteome and immunohistochemistry analysis was performed to assess changes at the transcriptional and translational levels. Finally, immunofluorescence was used to characterize the cell composition of the immune response and pathways involved in inflammation and fibrosis. Statistical analysis was performed using GraphPad Prism and RStudio for Welch ANOVA, Kruskal–Wallis and Dunnett’s T3 multiple comparison test. Stents cause significant inflammation and fibrosis of ureters. Gene set enrichment analysis confirmed fibrotic changes and tissue proliferation and suggests that epithelial–mesenchymal transition is a driver of fibrosis. Moreover, IL-6/JAK/STAT and TNFα via NF-κB signalling might contribute to chronic inflammation promoting a profibrotic environment. Immunostaining confirmed epithelial–mesenchymal transition in the urothelium and NF-κB expression in ureters stented for 14 days. Tissue alterations do not fully recover after 7 days. Histological evaluation showed that contralateral, unstented ureters are affected by mild inflammation. Our study showed that stenting has a significant impact on the ureter. Chronic inflammation and epithelial–mesenchymal transition are drivers of fibrosis, potentially impairing ureteral functionality in the long term. Furthermore, we observed mild inflammation in contralateral, unstented ureters. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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