In contrast, in UUO models, blocking DOT1L with EPZ5676 alleviates renal fibrosis by inhibiting multiple fibrosis pathways (including Smad3, EGFR, PDGFR and NF-κB pathway), up-regulating the expressions of renal protective factors such as PTEN, Klotho and Smad7,2 (Liu H. et al., 2019). The gene discussed is SMAD3; the disease is renal fibrosis.