20.500.12556/RUL-133685 Vitamin A rich diet diminishes early urothelial carcinogenesis by altering retinoic acid signaling Urinary bladder cancer is one of the leading malignancies worldwide, with the highest recurrence rates. A diet rich in vitamin A has proven to lower the risk of cancer, yet the molecular mechanisms underlying this effect are unknown. We found that vitamin A decreased urothelial atypia and apoptosis during early bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Vitamin A did not alter urothelial cell desquamation, differentiation, or proliferation rate. Genes like Wnt5a, involved in retinoic acid signaling, and transcription factors Pparg, Ppara, Rxra, and Hoxa5 were downregulated, while Sox9 and Stra6 were upregulated in early urothelial carcinogenesis. When a vitamin A rich diet was provided during BBN treatment, none of these genes was up- or downregulated; only Lrat and Neurod1 were upregulated. The lecithin retinol acyltransferase (LRAT) enzyme that produces all-trans retinyl esters was translocated from the cytoplasm to the nuclei in urothelial cells as a consequence of BBN treatment regardless of vitamin A rich diet. A vitamin A-rich diet altered retinoic acid signaling, decreased atypia and apoptosis of urothelial cells, and consequently diminished early urothelial carcinogenesis. urinary bladder early carcinogenesis vitamin A retinoic acid signaling apoptosis mehur early carcinogenesis vitamin A true false true Angleški jezik Slovenski jezik Članek v reviji 2021-12-09 09:20:57 2021-12-09 09:21:03 2022-09-13 03:52:04 0000-00-00 00:00:00 2020 0 0 19 str. iss. 7, art. 1712 Vol. 12 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006 2072-6694 10.3390/cancers12071712 21184515 RAZ_Zupancic_Dasa_2020.pdf RAZ_Zupancic_Dasa_2020.pdf 1 5D83F93A7ADEA75E9D03A5FBF87D92D1 4b8722cbb3d21a80df978d931e177a6991aa0e8f0162cab4d0d9b166e6934467 25ba4678-58c9-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151958 https://www.mdpi.com/2072-6694/12/7/1712 1 d70126ce-58c8-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151957 Medicinska fakulteta 0 0 0