Version 1
: Received: 3 July 2024 / Approved: 4 July 2024 / Online: 4 July 2024 (11:19:43 CEST)
How to cite:
Lewko, B.; Wodzinska, M.; Daca, A.; Płoska, A.; Obremska, K.; Kalinowski, L. Urolithin a Ameliorates the TGF Beta-Dependent Impairment of Podocytes Exposed to High Glucose. Preprints2024, 2024070378. https://doi.org/10.20944/preprints202407.0378.v1
Lewko, B.; Wodzinska, M.; Daca, A.; Płoska, A.; Obremska, K.; Kalinowski, L. Urolithin a Ameliorates the TGF Beta-Dependent Impairment of Podocytes Exposed to High Glucose. Preprints 2024, 2024070378. https://doi.org/10.20944/preprints202407.0378.v1
Lewko, B.; Wodzinska, M.; Daca, A.; Płoska, A.; Obremska, K.; Kalinowski, L. Urolithin a Ameliorates the TGF Beta-Dependent Impairment of Podocytes Exposed to High Glucose. Preprints2024, 2024070378. https://doi.org/10.20944/preprints202407.0378.v1
APA Style
Lewko, B., Wodzinska, M., Daca, A., Płoska, A., Obremska, K., & Kalinowski, L. (2024). Urolithin a Ameliorates the TGF Beta-Dependent Impairment of Podocytes Exposed to High Glucose. Preprints. https://doi.org/10.20944/preprints202407.0378.v1
Chicago/Turabian Style
Lewko, B., Katarzyna Obremska and Leszek Kalinowski. 2024 "Urolithin a Ameliorates the TGF Beta-Dependent Impairment of Podocytes Exposed to High Glucose" Preprints. https://doi.org/10.20944/preprints202407.0378.v1
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 ac-tivities 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 hours. 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 in HG expression of TGF-β receptors and activation of TGF-β signal transducer Smad2. Our results indicate that in podocytes cultured in conditions mimicking diabetic milieu, UA inhibits and reverses changes underlying podocytopenia in diabetic kidneys. Hence, UA should be considered as a po-tential therapeutic agent in podocytopathies.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
