Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
Emergency Department, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
J Cardiovasc Transl Res. 2021 Jun;14(3):525-537. doi: 10.1007/s12265-020-10081-w. Epub 2020 Nov 10.
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.
为了研究其对血管钙化的作用和分子调控机制，将 EPO 添加到体外培养的血管平滑肌细胞中，并通过腹腔注射到 SD 大鼠体内。通过茜素红染色和 ALP 活性测定 EPO 对 VSMC 钙化的影响。通过转录组测序筛选差异表达基因，并验证其关系和功能。我们发现 EPO 以剂量依赖的方式促进体外 VSMC 钙化和体内血液钙化。转录组测序共检测到 88 个上调基因和 59 个下调基因，其中与骨形成相关的基因表达明显增加，即 GATA6 转录因子、BMP2、RUNX2、OPN 和 OCN。双荧光素酶检测表明 GATA6 与 BMP2 启动子的结合促进了 BMP2 的转录。总之，研究结果表明，EPO 可以通过激活 GATA6/BMP2 信号轴增强 VSMCs 的钙化。
