To investigate its effect and molecular regulatory mechanism on vascular calcification, EPO was added to vascular smooth muscle cells cultured in vitro and injected intraperitoneally into SD rats. The effect of EPO on VSMC calcification was determined by alizarin red staining and ALP activity. Differentially expressed genes were screened by transcriptome sequencing and the relationship and function were verified. We found EPO promotes VSMC calcification in vitro and blood calcification in vivo in a dose-dependent manner. A total of 88 upregulated genes and 59 downregulated genes were detected in transcriptome sequencing, among which the expression of genes associated with bone formation exhibited a marked increase, namely the GATA6 transcription factor, BMP2, RUNX2, OPN, and OCN. Dual luciferase assay has indicated that the binding of GATA6 to BMP2 promoter facilitates the transcription of BMP2. Taken together, findings indicate that EPO can enhance the calcification of VSMCs by activating the GATA6/BMP2 signal axis.
Keywords: BMP2; Calcification; EPO; GATA6; VSMCs.