TGFB1 and chronic kidney disease: For example, SMAD3 and SMAD6 methylated changes were correlated with their transcriptional levels in samples of CKD pateints.172 The RAS protein activator-like 1 (RASAL1) hypermethylation was related to kidney fibrosis with the perpetuation of myofibroblast activation, where TGF-β mediated the hypermethylation of RASAL1 with DNMT1 effect in fibrogenesis.177 In whole-kidney biopsy and fibroblasts, hypermethylation and transcriptional silencing of RASAL1 was also related to severe fibrosis.