Fig. 4.

EZH2 affected diffuse cutaneous SSc EC angiogenesis through the Notch signaling pathway. (A) Heat map of angiogenesis-associated genes in SSc ECs after PBS or DZNep treatment. Only HEY2, a Notch target gene, was significantly up-regulated after DZNep treatment. (B) Relative mRNA expression of genes involved in Notch signaling after EZH2 inhibition by DZNep (5 μM, 48 h) in SSc ECs. Data are expressed as fold change versus PBS-treated cells. (C) Increased angiogenesis mediated by DZNep in SSc ECs was mediated by increased expression of Notch ligand DLL4, as DLL4 knockdown led to significant decrease in angiogenesis when cells were treated simultaneously with DZNep. (D) Genome browser tracks of the DLL4 locus along with ChIP-seq data for EZH2 and H3K27me3 in human umbilical endothelial cells generated by the ENCODE project. Results are expressed as mean ± SD. Unpaired t test or Kruskal–Wallis test were performed, and *P < 0.05 was considered significant.