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In this study, we investigated the contribution of histone H4 lysine 12 lactylation (H4K12la) to abnormal glycolysis and renal fibrogenesis in diabetic kidney disease (DKD) and evaluated sodium butyrate (NaB) as a potential therapeutic modulator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, db\/db mice (Bks. Cg\u2010\n                      <jats:sup>lepr<\/jats:sup>\n                      db\/\n                      <jats:sup>lepr<\/jats:sup>\n                      db) were employed as an in\u00a0vivo model of DKD, and high glucose\u2010treated human tubular epithelial cells (HK\u20102 cells) were used as an in\u00a0vitro model to investigate whether NaB exerts protective effects on DKD via modulating glycolysis and histone H4K12 lactylation\u2010mediated hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that H4K12la expression was significantly increased in diabetic kidneys, which was closely associated with enhanced glycolysis related fibrosis. Analysis of kidney biopsy tissues from patients with DKD confirmed that H4K12la levels were significantly elevated. CUT&amp;Tag sequencing in HK\u20102 cells revealed enrichment of H4K12la at genes involved in metabolic pathways, including the promoter region of\n                      <jats:italic>HIF1A<\/jats:italic>\n                      . In\u00a0vivo and in\u00a0vitro experiments demonstrated that NaB treatment suppressed the expression of glycolytic enzymes hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), reduced lactate production, improved renal function, and attenuated kidney fibrosis under diabetic conditions. Mechanistically, these effects were associated with decreased H4K12la enrichment at the\n                      <jats:italic>HIF1A<\/jats:italic>\n                      promoter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, our findings identify aberrant renal glycolysis and H4K12la as key drivers of diabetic renal fibrosis and suggest that NaB mitigates fibrosis by modulating glycolysis\u2010dependent H4K12la and HIF\u20101\u03b1 signalling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71166","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:49:12Z","timestamp":1785725352000},"page":"9518-9534","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sodium Butyrate Attenuates Renal Fibrosis by Regulating Glycolysis and Histone\n                    <scp>H4K12<\/scp>\n                    Lactylation in Diabetic Kidney Disease"],"prefix":"10.1111","volume":"28","author":[{"given":"Ping","family":"He","sequence":"first","affiliation":[{"name":"Department of Nephrology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-0795","authenticated-orcid":false,"given":"Mingxiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2641-3102","authenticated-orcid":false,"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Second Hospital of Jilin University  Changchun Jilin Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital of Anhui Medical University  Hefei Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Shengjing Hospital of China Medical University  Shenyang Liaoning Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First Hospital of China Medical University  Shenyang Liaoning Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Tang","sequence":"additional","affiliation":[{"name":"Precision Research Center for Refractory Diseases Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuling","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,2]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"IDF Diabetes Atlas","author":"Magliano D. 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