{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:45:26Z","timestamp":1791895526700,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100015661","name":"UCB Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010016","name":"Nottingham Trent University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>\n                    Urinary extracellular vesicles (uEVs) are an attractive source of biomarkers as their cargo of proteins, nucleic acids and lipids reflects cell pathophysiology. The physical properties of uEVs such as their electrical nature measured by the zeta potential (charge at the interface of vesicle and liquid) are seldom explored although their understanding may lead to translational applications of EVs in clinical settings. In diabetes and diabetic kidney disease (DKD), post\u2010translational modifications resulting from loss of glycocalyx (diabetes) and gain of extracellular matrix components (tissue fibrosis) could potentially affect the electrical charge of pathologically relevant EVs. DKD cohorts obtained by adhering to industry\u2010standard reproducible criteria were stratified into stable and progressive disease based on estimated glomerular filtration rate (eGFR) loss and compared to nonkidney disease diabetic and healthy controls. Surface charge analysis revealed a significant difference in the zeta potential of large uEVs between the diabetic and healthy cohorts, as well as between the diabetic and DKD\u2010progressive cohorts. These differences are mechanistically consistent with pathological alterations observed in heparan sulfate (HS) content. Accordingly, uEVs from DKD patients exhibited higher HS levels than those from diabetic individuals, as assessed by SP\u2010IRIS\/\n                    <jats:sc>ExoView<\/jats:sc>\n                    using HS\u2010binding capture. Comparative proteomic analysis further demonstrated an increased abundance of the sulfated glycosaminoglycan lumican in DKD uEVs relative to diabetes, consistent with its reported upregulation in early fibrotic stages of DKD. Notably, our findings indicate for the first time that the zeta potential of large uEVs may be predictive of the progression of diabetes into DKD.\n                  <\/jats:p>","DOI":"10.1111\/febs.70764","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:49:10Z","timestamp":1791892150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Surface charge alterations in urinary extracellular vesicles mirror diabetic kidney disease pathophysiology"],"prefix":"10.1111","author":[{"given":"Melanie","family":"Tepu\u0161","sequence":"first","affiliation":[{"name":"Centre for Systems Health and Integrated Metabolic Research, School of Science and Technology Nottingham Trent University  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Savoca","sequence":"additional","affiliation":[{"name":"Centre for Systems Health and Integrated Metabolic Research, School of Science and Technology Nottingham Trent University  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mabrouka","family":"Maamra","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, School of Medicine University of Sheffield  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor J.","family":"Meehan","sequence":"additional","affiliation":[{"name":"Centre for Systems Health and Integrated Metabolic Research, School of Science and Technology Nottingham Trent University  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios S.","family":"Goumenos","sequence":"additional","affiliation":[{"name":"Department of Nephrology Patras University Hospital  Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Johnson","sequence":"additional","affiliation":[{"name":"Mestag Therapeutics Limited, Science Cambridge  UK"},{"name":"UCB Pharma  Slough UK"},{"name":"Academic Nephrology Unit, Medical School University of Sheffield  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9153-8997","authenticated-orcid":false,"given":"Elisabetta A. 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