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Due to their multidirectional effects, including anti-inflammatory, antioxidant, anti-cancer, neuroprotective, and antiglycative properties, urolithins are potential novel therapeutic agents. In this study, while considering the future possibility of using urolithins to improve podocyte function in diabetes, we assessed the results of exposing mouse podocytes cultured in normal (NG, 5.5 mM) and high (HG, 25 mM) glucose concentrations to urolithin A (UA) and urolithin B (UB). Podocytes metabolized UA to form glucuronides in a time-dependent manner; however, in HG conditions, the metabolism was lower than in NG conditions. In HG milieu, UA improved podocyte viability more efficiently than UB and reduced the reactive oxygen species level. Both types of urolithins showed cytotoxic activity at high (100 \u00b5M) concentration. The UA upregulated total and surface nephrin expression, which was paralleled by enhanced nephrin internalization. Regulation of nephrin turnover was independent of ambient glucose concentration. We conclude that UA affects podocytes in different metabolic and functional aspects. With respect to its pro-survival effects in HG-induced toxicity, UA could be considered as a potent therapeutic candidate against diabetic podocytopathy.<\/jats:p>","DOI":"10.3390\/cells11162471","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T02:42:53Z","timestamp":1660099373000},"page":"2471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose"],"prefix":"10.3390","volume":"11","author":[{"given":"Milena","family":"Kotewicz","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miros\u0142awa","family":"Krauze-Baranowska","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1485-3090","authenticated-orcid":false,"given":"Agnieszka","family":"Daca","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Rheumatology, Faculty of Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0408-5262","authenticated-orcid":false,"given":"Agata","family":"P\u0142oska","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Diagnostics-Fahrenheit Biobank BBMRI, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylwia","family":"Godlewska","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-1592","authenticated-orcid":false,"given":"Leszek","family":"Kalinowski","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Diagnostics-Fahrenheit Biobank BBMRI, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, Poland"},{"name":"BioTechMed Centre, Department of Mechanics of Materials and Structures, Gdansk University of Technology, 80-233 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4512-9559","authenticated-orcid":false,"given":"Barbara","family":"Lewko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. 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