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Abstract
Increased activity of transforming growth factor-beta (TGF-β) is a key factor mediating kidney impairment in diabetes. Glomerular podocytes, the crucial component of the renal filter, are a direct target of TGF-β action, resulting in irreversible cell loss and progression of chronic kidney disease (CKD). Urolithin A (UA) is a member of the family of polyphenol metabolites produced by gut microbiota from ellagitannins and ellagic acid-rich foods. The broad spectrum of biological activities of UA makes it a promising candidate for the treatment of podocyte disorders. In this in vitro study, we investigated whether UA influences the changes exerted in podocytes by TGF-β and high glucose. Following a 7-day incubation in normal (NG, 5.5 mM) or high (HG, 25 mM) glucose, the cells were treated with UA and/or TGF-β1 for 24 h. HG and TGF-β1, each independent and in concert reduced expression of nephrin, increased podocyte motility, and up-regulated expression of b3 integrin and fibronectin. These typical-for-epithelial-to-mesenchymal transition (EMT) effects were inhibited by UA in both HG and NG conditions. UA also reduced the typically elevated HG expression of TGF-β receptors and activation of the TGF-β signal transducer Smad2. Our results indicate that in podocytes cultured in conditions mimicking the diabetic milieu, UA inhibits and reverses changes underlying podocytopenia in diabetic kidneys. Hence, UA should be considered as a potential therapeutic agent in podocytopathies.
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Authors (6)
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Barbara Lewko
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Milena Wodzińska
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Agnieszka Daca
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Agata Płoska
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Katarzyna Obremska
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- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/jpm14090914
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
Journal of Personalized Medicine
no. 14,
ISSN: 2075-4426 - Language:
- English
- Publication year:
- 2024
- Bibliographic description:
- Lewko B., Wodzińska M., Daca A., Płoska A., Obremska K., Kalinowski L.: Urolithin A Ameliorates the TGF Beta-Dependent Impairment of Podocytes Exposed to High Glucose// Journal of Personalized Medicine -Vol. 14,iss. 9 (2024), s.914-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/jpm14090914
- Sources of funding:
-
- This research was funded by the Ministry of Science and Higher Education, grant no. 2/566516/SPUB/SP/2023 to L.K.
- Verified by:
- Gdańsk University of Technology
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