{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:53:23Z","timestamp":1792803203063,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"37","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK076077"],"award-info":[{"award-number":["R01DK076077"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK087635"],"award-info":[{"award-number":["R01DK087635"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50DK114786"],"award-info":[{"award-number":["P50DK114786"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK105821"],"award-info":[{"award-number":["R01DK105821"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK132630"],"award-info":[{"award-number":["R01DK132630"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n The mechanisms by which metabolic stress drives epigenetic dysregulation and fibrosis in chronic kidney disease (CKD) remain incompletely understood. Using quantitative histone proteomics in murine fibrosis models, we uncovered a selective increase in\u00a0 histone H3 lysine 27 acetylation (H3K27ac) as a conserved epigenetic feature. Unbiased metabolomics revealed citrate accumulation, nominating ATP\u2010citrate lyase (ACLY) as a driver of acetyl\u2010CoA\u2010dependent histone acetylation. In murine models of folic acid and unilateral ureteral obstruction, ACLY expression, acetyl\u2010CoA levels, and H3K27ac were increased in injured kidneys. Tubule\u2010specific\n Acly<\/jats:italic>\n deletion reduced acetyl\u2010CoA, H3K27ac, and attenuated tubulointerstitial fibrosis. Chromatin accessibility profiling revealed that loss of\n Acly<\/jats:italic>\n decreased accessibility at pro\u2010inflammatory loci, including\n Jak1<\/jats:italic>\n and\n Jak2<\/jats:italic>\n , with reduced transcriptional output. These transcriptional and epigenetic signatures were observed in human CKD samples, where higher ACLY expression correlated with worse kidney function and increased JAK1\/2 expression. Notably, ACLY inhibitors, including bempedoic acid and BMS\u2010303141 recapitulated the antifibrotic effects of\n Acly<\/jats:italic>\n deletion in vivo in mice, supporting the therapeutic repurposing of ACLY inhibitors for CKD. Together, our findings position ACLY as a key metabolic\u2010epigenetic checkpoint of kidney fibrosis and a promising, druggable target for halting CKD progression.\n <\/jats:p>","DOI":"10.1002\/advs.75247","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T19:19:12Z","timestamp":1776367152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["ACLY\u2010Driven Metabolic Reprogramming Promotes Histone Acetylation and Inflammation\u2010Associated Fibrosis in Chronic Kidney Disease"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4152-4663","authenticated-orcid":false,"given":"Chunxiu","family":"Du","sequence":"first","affiliation":[{"name":"Institutes for Diabetes Obesity and Metabolism Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Renal Electrolyte & Hypertension Division 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