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Runt\u2010related transcription factor 1 (Runx1), a highly conserved regulator of gene expression, orchestrates diverse cellular signaling pathways. Here, we identify Runx1 as a critical driver of cyst growth in ADPKD. Runx1 expression is markedly upregulated in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    mutant renal epithelial cells and kidney tissues through a cAMP\u2010dependent mechanism. Pharmacological inhibition of Runx1 with its selective inhibitor, Ro5\u20103335, significantly attenuates cyst progression in both rapidly and slowly progressive\n                    <jats:italic>Pkd1<\/jats:italic>\n                    mouse models. Mechanistically, Runx1 enhances proliferation of cyst\u2010lining epithelial cells by activating the AKT\u2013mTOR, MAPK, and STAT3 signaling cascades, while suppressing p53\u2010mediated apoptosis. Moreover, Runx1 promotes macrophage infiltration and inflammatory responses via NF\u2010\u03baB activation and aggravates interstitial fibrosis through the TGF\u2010\u03b2\/Smad2 pathway. Collectively, these findings uncover Runx1 as a pivotal regulator of cystic disease progression and highlight it as a promising therapeutic target for ADPKD.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600741r","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:43:54Z","timestamp":1787672634000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Runx1 Slows Cyst Growth in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1096","volume":"40","author":[{"given":"Yueyue","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Nephrology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai 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