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A better understanding of the pathogenesis of AKI may lead to new therapeutic approaches. Kidney transcriptomics of folic acid\u2010induced AKI (FA\u2010AKI) in mice identified\n                    <jats:italic>Runx1<\/jats:italic>\n                    as the most upregulated RUNX family gene. We then examined the expression of RUNX1 in FA\u2010AKI, in bacterial lipopolysaccharide (LPS)\u2010induced cytokine storm\u2010AKI (CS\u2010AKI), and in human AKI. In cultured mouse tubule cells, we explored the expression and role of RUNX1 in response to the cytokine TWEAK or LPS. A chemical inhibitor of RUNX1 (Ro5\u20103335) was used in animal models of AKI to test its potential as a therapeutic target. RUNX1 overexpression in FA\u2010AKI was validated at the mRNA and protein levels and localized mainly to tubule cell nuclei. CS\u2010AKI also upregulated kidney RUNX1. Increased tubule and interstitial RUNX1 expression were also observed in human AKI. In cultured mouse tubule cells, the pro\u2010inflammatory cytokine TWEAK and LPS increased RUNX1 and IL\u20106 expression. Mechanistically, RUNX1 bound to the\n                    <jats:italic>Il6<\/jats:italic>\n                    gene promoter and RUNX1 targeting with the chemical inhibitor Ro5\u20103335, or a specific small interfering RNA (siRNA), prevented the TWEAK\u2010 and LPS\u2010induced upregulation of IL6 through a RUNX1\/NF\u03baB1 p50 pathway.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , preventive Ro5\u20103335 improved kidney function and reduced inflammation in FA\u2010AKI and CS\u2010AKI. However, Ro5\u20103335 administration after the insult only improved kidney function in CS\u2010AKI. Kidney transcriptomics identified inflammatory genes and transcription factor mRNAs such as\n                    <jats:italic>Yap1<\/jats:italic>\n                    and\n                    <jats:italic>Trp53<\/jats:italic>\n                    as key targets of Ro5\u20103335 in CS\u2010AKI. In conclusion, RUNX1 contributes to AKI by driving the expression of genes involved in inflammation and represents a novel therapeutic target in AKI. \u00a9 2024 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6355","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T22:10:48Z","timestamp":1730239848000},"page":"396-410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Runt\u2010related transcription factor 1 (\n                    <scp>RUNX1<\/scp>\n                    ) is a mediator of acute kidney injury"],"prefix":"10.1002","volume":"264","author":[{"given":"Miguel","family":"Fontecha\u2010Barriuso","sequence":"first","affiliation":[{"name":"Laboratorio de 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