Fig. 6.

The mechanism of diabetes promoting myocardial fibrosis via AMP-activated protein kinase (AMPK)/enhancer of zeste homolog 2 (EZH2)/peroxisome proliferator-activated receptor γ (PPAR-γ) signaling pathway. Under normal glucose, phosphorylation of AMPK phosphorylates EZH2, which inhibits the trimethylation activity EZH2, leading to expression of PPAR-γ and inhibition of myocardial fibroblasts activation. Under the condition of diabetics, high glucose inactivates AMPK, increases trimethylation activity EZH2 by reducing the phosphorylation of EZH2 at T311, which represses transcription of PPAR-γ and suppressed diabetic fibrosis. P, phosphorylation; EED, embryonic ectoderm development; SUZ12, suppressor of zest 12; H3K27me3, histone H3 lysine 27 trimethylation; TGF-β, transforming growth factor-β; α-SMA, α-smooth muscle actin; GSK126, competitive inhibitor of PRC2.