Gestational diabetes mellitus is one of the causes of abnormal embryonic heart development, but the mechanism is still poor. This study investigated the regulatory mechanism and role of SOX11 in congenital heart abnormality in a hyperglycemic environment. Immunohistochemistry, Western blotting, and quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) showed decreased SOX11 protein and messenger RNA (mRNA) levels in the heart tissue of diabetic offspring compared with the control group. A Sequenom EpiTYPER MassArray showed that methylation sites upstream in SOX11 region 1 were increased in the diabetic group compared with the control group. Luciferase reporter assays and qRT‐PCR showed that Dnmt3b overexpression decreased SOX11 promoter activity and its mRNA level, whereas Dnmt3a had little effect on regulating SOX11 expression. Furthermore, we found that Dnmt3L cooperated with Dnmt3b to regulate SOX11 gene expression. Additionally, the function of SOX11 silencing was analyzed by using small interfering RNA‐mediated knockdown. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and apoptotic assays showed that SOX11 downregulation inhibited cell viability and induced apoptosis in cardiomyocytes. Overexpression of the SOX11 gene suppressed cardiomyocytes apoptosis after high glucose treatment. We identified a novel epigenetic regulatory mechanism of SOX11 during heart development in a hyperglycemic environment and revealed a distinct role of SOX11 in mediating cardiomyocytes viability and apoptosis.

中文翻译：

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高血糖环境下胎儿心脏组织中SOX11的下调介导心肌细胞凋亡。

妊娠糖尿病是胚胎心脏异常发育的原因之一，但机制仍较差。这项研究调查了高血糖环境中先天性心脏异常中SOX11的调节机制和作用。免疫组化，Western印迹和定量逆转录聚合酶链反应（qRT-PCR）显示，与对照组相比，糖尿病后代心脏组织中SOX11蛋白和信使RNA（mRNA）水平降低。Sequenom EpiTYPER MassArray显示，与对照组相比，糖尿病组中SOX11 1区上游的甲基化位点增加。荧光素酶报告基因分析和qRT-PCR结果表明，Dnmt3b过表达降低了SOX11启动子活性及其mRNA水平，而Dnmt3a对调节SOX11表达的影响很小。此外，我们发现Dnmt3L与Dnmt3b协同调节SOX11基因表达。另外，使用小的干扰RNA介导的敲低分析了SOX11沉默的功能。3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物和凋亡分析表明SOX11的下调抑制了心肌细胞的活力并诱导了其凋亡。高葡萄糖处理后，SOX11基因的过表达抑制了心肌细胞的凋亡。我们确定了高血糖环境中心脏发育过程中SOX11的新型表观遗传调控机制，并揭示了SOX11在介导心肌细胞活力和凋亡中的独特作用。通过使用小干扰RNA介导的敲低分析SOX11沉默的功能。3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物和凋亡分析表明SOX11的下调抑制了心肌细胞的活力并诱导了其凋亡。高葡萄糖处理后，SOX11基因的过表达抑制了心肌细胞的凋亡。我们确定了高血糖环境中心脏发育过程中SOX11的新型表观遗传调控机制，并揭示了SOX11在介导心肌细胞活力和凋亡中的独特作用。通过使用小干扰RNA介导的敲低分析SOX11沉默的功能。3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物和凋亡分析表明SOX11的下调抑制了心肌细胞的活力并诱导了其凋亡。高葡萄糖处理后，SOX11基因的过表达抑制了心肌细胞的凋亡。我们确定了高血糖环境中心脏发育过程中SOX11的新型表观遗传调控机制，并揭示了SOX11在介导心肌细胞活力和凋亡中的独特作用。高葡萄糖处理后，SOX11基因的过表达抑制了心肌细胞的凋亡。我们确定了高血糖环境中心脏发育过程中SOX11的新型表观遗传调控机制，并揭示了SOX11在介导心肌细胞活力和凋亡中的独特作用。高葡萄糖处理后，SOX11基因的过表达抑制了心肌细胞的凋亡。我们确定了高血糖环境中心脏发育过程中SOX11的新型表观遗传调控机制，并揭示了SOX11在介导心肌细胞活力和凋亡中的独特作用。