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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,4,29]]},"abstract":"<jats:p>\n                    Inflammation plays an essential role in eliminating microbial pathogens and repairing tissues, while sustained inflammation accelerates kidney damage and disease progression. Therefore, understanding the mechanisms of the inflammatory response is vital for developing therapies for inflammatory kidney diseases like acute kidney injury (AKI), which currently lacks effective treatment. Here, we identified N-acetyltransferase 10 (\n                    <jats:italic>NAT10<\/jats:italic>\n                    ) as an important regulator for acute inflammation.\n                    <jats:italic>NAT10<\/jats:italic>\n                    , the only known \u201cwriter\u201d protein for N4-acetylcytidine (ac4C) acetylation, is elevated in renal tubules across various AKI models, human biopsies, and cultured tubular epithelial cells (TECs). Conditional knockout (cKO) of\n                    <jats:italic>NAT10<\/jats:italic>\n                    in mouse kidneys attenuates renal dysfunction, inflammation, and infiltration of macrophages and neutrophils, whereas its conditional knock-in (cKI) exacerbates these effects. Mechanistically, our findings from ac4C-RIP-seq and RNA-seq analyses revealed that NAT10-mediated ac4C acetylation enhances the mRNA stability of a range of key chemokines, including C-C motif chemokine ligand 2 (\n                    <jats:italic>CCL2<\/jats:italic>\n                    ) and C-X-C motif chemokine ligand 1(\n                    <jats:italic>CXCL1<\/jats:italic>\n                    ), promoting macrophage and neutrophil recruitment and accelerating renal inflammation. Additionally,\n                    <jats:italic>CCL2<\/jats:italic>\n                    and\n                    <jats:italic>CXCL1<\/jats:italic>\n                    neutralizing antibodies or their receptor inhibitors, abrogated renal inflammation in\n                    <jats:italic>NAT10<\/jats:italic>\n                    -overexpression TECs or\n                    <jats:italic>NAT10<\/jats:italic>\n                    -cKI mice. Importantly, inhibiting\n                    <jats:italic>NAT10<\/jats:italic>\n                    , either through Adeno-associated virus 9 (AAV9)-mediated silencing or pharmacologically with our found inhibitor Cpd-155, significantly reduces renal inflammation and injury. Thus, targeting the\n                    <jats:italic>NAT10\/CCL2\/CXCL1<\/jats:italic>\n                    axis presents a promising therapeutic strategy for treating inflammatory kidney diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2418409122","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T13:36:04Z","timestamp":1745328964000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["<i>NAT10<\/i>\n                    exacerbates acute renal inflammation by enhancing N4-acetylcytidine modification of the CCL2\/CXCL1 axis"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9566-6539","authenticated-orcid":false,"given":"Jia-nan","family":"Wang","sequence":"first","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of 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Wang , PIWI-interacting RNA HAAPIR regulates cardiomyocyte death after myocardial infarction by promoting NAT10-mediated ac(4)C acetylation of Tfec mRNA. Adv. Sci. (Weinh.) 9, e2106058 (2022).","journal-title":"Adv. Sci. 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Chen , NAT10\/ac4C\/FOXP1 promotes malignant progression and facilitates immunosuppression by reprogramming glycolytic metabolism in cervical cancer. Adv. Sci. (Weinh.) 10, e2302705 (2023).","journal-title":"Adv. Sci. (Weinh.)"},{"key":"e_1_3_4_48_2","unstructured":"J. -n. Wang NAT10 Exacerbates Acute Renal Inflammation by Enhancing N4-Acetylcytidine Modification of the CCL2\/CXCL1 Axis. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE286352. 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