{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:56:18Z","timestamp":1790848578918,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic foot ulcers (DFUs) frequently complicate diabetes. Ubiquitin\u2010specific protease 30 (USP30), a key deubiquitinating enzyme, is implicated in diverse diseases. This study explores USP30's effects and mechanisms on DFUs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Tumor necrosis factor receptor\u2010associated factor 6 (TRAF6), USP30, GPX4, and SLC7A11 protein levels were determined using western blot. TRAF6 mRNA level was assessed using real\u2010time RT\u2010qPCR. Cell proliferation and mortality were evaluated via the 5\u2010Ethynyl\u20102\u2032\u2010deoxyuridine assay and TdT\u2010mediated dUTP nick end labeling, respectively. Intracellular ferrous ion levels, malondialdehyde concentrations, and superoxide dismutase activity were measured with specialized cell metabolism kits, while intracellular reactive oxygen species levels were detected by flow cytometry. Cell migration was evaluated through wound healing assays, and tube formation was quantified using the tube formation method. Co\u2010immunoprecipitation was conducted to validate USP30's regulatory effect on TRAF6 ubiquitination. Mouse models of DFU were established for\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TRAF6 was highly expressed in human umbilical vein endothelial cells (HUVECs) induced by high glucose (HG). TRAF6 knockdown enhanced cell proliferation, inhibited apoptosis and ferroptosis, and promoted cell migration and tubule formation in these cells. In HG\u2010induced HUVECs, USP30 was also overexpressed and stabilized TRAF6 expression through deubiquitination. USP30 knockdown alleviated HG\u2010induced injury in HUVECs by targeting TRAF6. Moreover, USP30 knockdown accelerated DFU wound healing and inhibited ferroptosis\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>USP30 stabilizes TRAF6 via deubiquitination, triggering ferroptosis and suppressing angiogenesis, which ultimately impedes wound healing in DFU. This offers direct evidence for the modulatory role of USP30 in DFU.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70384","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T15:06:32Z","timestamp":1784559992000},"page":"1708-1725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>USP30<\/scp>\n                    inhibits wound healing in diabetic foot ulcers by promoting\n                    <scp>TRAF6<\/scp>\n                    \u2010induced ferroptosis and angiogenesis inhibition"],"prefix":"10.1111","volume":"17","author":[{"given":"Jingjing","family":"Yuan","sequence":"first","affiliation":[{"name":"Endocrinology Department The 970th Hospital of the Joint Service Support Force of the Chinese People's Liberation Army  Yantai 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