Lastly and impressively, we further investigated the underlying mechanism behind the low expression of TEFB in UUO-induced renal fibrosis, and clearly revealed that TFEB suppression was due to DNMT3a-associated TFEB promoter hypermethylation, which could be effectively recovered by 5-Aza-2'-deoxycytidine (5A-za) to alleviate renal fibrosis pathogenesis. Here, TFEB is linked to renal fibrosis.