Vitamin A-enriched diet increases urothelial cell proliferation by upregulating Itga3 and Areg after cyclophosphamide-induced injury in mice

Dragar, Brina (author), Kranjc Brezar, Simona (author), Čemažar, Maja (author), Jesenko, Tanja (author), Romih, Rok (author), Erdani-Kreft, Mateja (author), Kuret, Tadeja (author), Zupančič, Daša (author)

Vitamin A (VitA) is an essential nutrient, affecting many cell functions, such as proliferation, apoptosis, and differentiation, all of which are important for the regeneration of various tissues. In this study, we investigated the effects of a VitA-enriched diet on the regeneration of the urothelium of the urinary bladder in mice after cyclophosphamide (CP)-induced injury. Female mice were fed VitA-enriched and normal diet for 1 week before receiving an intraperitoneal injection of CP (150 mg/kg). Urinary bladders were removed 1 and 3 days after CP. On Day 1, RNA sequencing showed that VitA upregulated two Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways: the cell cycle and the PI3K-Akt pathway. This was confirmed by qPCR, which showed significantly increased expression of the Itga3 and Areg genes. In addition, the effect of VitA on the proliferation of urothelial cells was analyzed by immunohistochemistry of Ki-67, which confirmed an increased proliferation rate. No significant effects of the VitA-enriched diet were observed on the expression of apoptosis-related genes and on differentiation-related markers of superficial urothelial cells. Our results suggest that a VitA-enriched diet improves early urothelial regeneration after CP-induced injury by promoting cell proliferation.

• Language: English
• Keywords: apoptosis, cyclophosphamide, differentiation, injury, proliferation, urinary bladder, urothelium, vitamin A
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 14 str.
• Numbering: Vol. 69, iss. 9, art. e70045
• PID: 20.500.12556/RUL-169064
• UDC: 616-006:576
• ISSN on article: 1613-4133
• DOI: 10.1002/mnfr.70045
• COBISS.SI-ID: 232348419
• Publication date in RUL: 09.05.2025

Record is a part of a journal

• Title: Molecular nutrition & food research
• Shortened title: Mol. nut. food res.
• Publisher: Wiley
• ISSN: 1613-4133
• COBISS.SI-ID: 512824345

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: apoptoza, ciklofosfamid, diferenciacija, poškodba, širjenje, sečni mehur, urotelija, vitamin A