{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:12:06Z","timestamp":1790327526328,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470759"],"award-info":[{"award-number":["82470759"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000697"],"award-info":[{"award-number":["82000697"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ3022"],"award-info":[{"award-number":["2024JJ3022"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>NOP2\/Sun RNA methyltransferase family member 4 (NSUN4)\u2010mediated 5\u2010methylcytosine (m5C) modification has been implicated in diabetes\u2010related diseases. However, its role and molecular mechanism in diabetic nephropathy (DN) remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>DN mouse model was constructed by injecting with streptozotocin (STZ). High glucose (HG)\u2010induced HK\u20102 cells were used to establish a cellular model of DN. The levels of NSUN4, SMAD ubiquitination regulatory factor 1 (SMURF1), calcium\/calmodulin\u2010dependent protein kinase 1 (CAMK1), and mitochondrial\u2010related proteins were analyzed using qRT\u2010PCR, western blot, or immunohistochemical staining. Renal injury in mice was evaluated using relevant kits and histological staining. Cell apoptosis, ROS production and proliferation were examined by TUNEL, dihydroethidium, MitoSOX Red and EdU staining. The interaction between SMURF1 and Aly\/REF export factor (ALYREF) or CAMK1 was confirmed by RNA immunoprecipitation, Co\u2010IP and ubiquitination assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Upregulation of NSUN4 increased the m5C level in DN. Knockout of NSUN4 alleviated STZ\u2010induced renal injury in mice by repressing renal tubule cell mitochondrial fission and promoting mitochondrial fusion. NSUN4 downregulation reduced mitochondrial fission and promoted mitochondrial fusion to relieve HG\u2010induced HK\u20102 cell apoptosis. NSUN4\u2010mediated m5C modification promoted SMURF1 mRNA stability by regulating ALYREF. SMURF1 overexpression rescued the suppressive effect of NSUN4 knockdown on cell mitochondrial fission and apoptosis. Besides, SMURF1 facilitated the ubiquitination and degradation of CAMK1. Furthermore, sh\u2010CAMK1 abolished the inhibitory effect of sh\u2010SMURF1 on cell mitochondrial fission and apoptosis. Meanwhile, downregulation of NSUN4 relieved STZ\u2010induced renal injury in DN mice by reducing mitochondrial fission via the SMURF1\/CAMK1 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NSUN4\u2010mediated upregulation of SMURF1 promoted mitochondrial fission to accelerate DN progression via increasing CAMK1 ubiquitination. The discovery of the NSUN4\/SMURF1\/CAMK1 axis provides new insights into DN pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70783","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:58:26Z","timestamp":1787900306000},"source":"Crossref","is-referenced-by-count":0,"title":["NSUN4\u2010dependent m5C modification facilitates mitochondrial fission to accelerate diabetic nephropathy process via regulating SMURF1\/CAMK1 axis"],"prefix":"10.1002","volume":"16","author":[{"given":"Danyi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Nephrology The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification  Changsha City China"},{"name":"National Clinical Research Center for Metabolic Diseases The Second Xiangya Hospital Central South University  Changsha City 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