In summary, our data demonstrated that H3K4me and H3K9me as well as HMT SET7/9 occupancy changed significantly at p21 gene promoter in the glomeruli of type 1 diabetic rats and HG-induced RMCs, resulting in parallel increases in the p21 gene expression related to cellular hypertrophy, and that TGF-β1-specific antibody could reverse HG-induced changes in vitro, all of which are related to the pathogenesis of DN, suggesting that HKme and SET7/9 could act as potential therapeutic targets for cellular hypertrophy of DN and TGF-β1-specific antibody could be clinical agent for DN therapy. Here, TGFB1 is linked to liver dysplastic nodule.