{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:57:10Z","timestamp":1787327830085,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["252300423858"],"award-info":[{"award-number":["252300423858"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["252300423190"],"award-info":[{"award-number":["252300423190"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Diabetic kidney disease (DKD) is characterized by progressive tubular injury, yet the mechanisms linking metabolic stress to organelle dysfunction remain unclear. Here, utilizing human renal biopsies, db\/db and high\u2010fat diet with streptozotocin\u2010induced diabetic mouse models, and cultured renal tubular epithelial cells (RTECs) exposed to 30\u00a0mM glucose, we demonstrate that impaired pexophagy drives peroxisomal dysfunction and tubular damage in DKD. Diabetic conditions induced marked accumulation of the peroxisomal membrane protein PMP70 (encoded by ABCD3\/Abcd3) in RTECs, reflecting impaired peroxisomal turnover. We identified ubiquitin\u2010specific peptidase 30 (USP30) as a contributor of this process. Expression profiling and localization analyses revealed that USP30 expression was significantly elevated in vivo and in vitro under high\u2010glucose conditions and predominantly localized to RTECs. Global genetic depletion of USP30 restored peroxisomal function and metabolic homeostasis, enhanced pexophagy, and attenuated tubular injury. Mechanistically, USP30 antagonized the ubiquitination of the peroxisomal import receptor PEX5, thereby suppressing pexophagy. Furthermore, deletion of the essential autophagy factor ATG5 abolished the protective effects of USP30 deficiency. These findings reveal a critical role of USP30 mediated regulation of pexophagy in DKD and suggest that USP30 may serve as an experimental intervention target to alleviate tubular injury in DKD.<\/jats:p>","DOI":"10.1002\/advs.77161","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:52:12Z","timestamp":1787323932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["USP30\u2010Mediated Deubiquitination of PEX5 Suppresses Pexophagy to Drive Tubular Injury in Diabetic Kidney Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6507-2385","authenticated-orcid":false,"given":"Jia","family":"Li","sequence":"first","affiliation":[{"name":"Research Institute of Nephrology Zhengzhou University The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Traditional Chinese Medicine Integrated Department of Nephrology The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Henan Province Research Center for Kidney Disease  Zhengzhou People's Republic of China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province  Zhengzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0317-8931","authenticated-orcid":false,"given":"Chaoyang","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Department of Urology, Henan Children's Hospital Children's Hospital Affiliated to Zhengzhou University  Zhengzhou People's Republic of 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0632-1414","authenticated-orcid":false,"given":"Furong","family":"Zhai","sequence":"additional","affiliation":[{"name":"Research Institute of Nephrology Zhengzhou University The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Traditional Chinese Medicine Integrated Department of Nephrology The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Henan Province Research Center for Kidney Disease  Zhengzhou People's Republic of China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province  Zhengzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Ren","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Kidney Diseases Jinling Hospital Nanjing 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Zhengzhou University The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Traditional Chinese Medicine Integrated Department of Nephrology The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Henan Province Research Center for Kidney Disease  Zhengzhou People's Republic of China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province  Zhengzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Institute of Nephrology Zhengzhou University The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Traditional Chinese Medicine Integrated Department of Nephrology The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Henan Province Research Center for Kidney Disease  Zhengzhou People's Republic of China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province  Zhengzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2916-8371","authenticated-orcid":false,"given":"Zhangsuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Institute of Nephrology Zhengzhou University The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Traditional Chinese Medicine Integrated Department of Nephrology The First Affiliated Hospital of Zhengzhou University  Zhengzhou People's Republic of 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