Renal fibrosis is widely considered a common mechanism leading to end-stage renal failure. Epithelial-to-mesenchymal transition (EMT) plays important roles in the pathogenesis of renal fibrosis. Runt-related transcription factor 1 (RUNX1) plays a vital role in hematopoiesis via Endothelial-to-Hematopoietic Transition (EHT), a process that is conceptually similar to EMT, but its role in EMT and renal fibrosis is unclear. Here, we demonstrate that RUNX1 is overexpressed in the processes of TGF-beta-induced partial EMT and renal fibrosis and that the expression level of RUNX1 is SMAD3-dependent.Knockdown of RUNX1 attenuated both TGE-beta-induced phenotypic changes and the expression levels of EMT marker genes in renal tubular epithelial cells (RTECs). In addition, overexpression of RUNXI promoted the expression of EMT marker genes in renal tubular epithelial cells. Moreover, RUNXI promoted TGF-beta-induced partial EMT by increasing transcription of the PI3K subunit p110 delta, which mediated Akt activation. Specific deletion of Runx1 in mouse RTECs attenuated renal fibrosis, which was induced by both unilateral ureteral obstruction (UUO) and folic acid (FA) treatment. These findings suggest that RUNX1 is a potential target for preventing renal fibrosis. (C) 2018 The Authors. Published by Elsevier B.V.