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Thymine DNA glycosylase is a key regulator of CaMKIIgamma expression and vascular smooth muscle phenotype

机译:胸腺嘧啶DNA糖基酶是Camkiigamma表达和血管平滑肌表型的关键调节剂

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With the use of methylated cytosine immunoprecipitation, the rat Camk2g promoter was found hypomethylated in differentiated VSM, whereas injury- or cell culture-induced VSM dedifferentiation coincided with Camk2g promoter methylation and decreased expression. We report for the first time that VSM cell phenotype switching is accompanied by marked induction of thymine DNA glycosylase (TDG) protein and mRNA expression in injured arteries in vivo and in cultured VSM synthetic phenotype cells. Silencing Tdg in VSM promoted expression of CaMKIIgamma and differentiation markers, including myocardin, and inhibited VSM cell proliferation and injury-induced neointima formation. This study indicates that CaMKIIgamma expression in VSM is regulated by cytosine methylation/demethylation and that TDG is an important determinant of this process and, more broadly, VSM phenotype switching and function.
机译:通过使用甲基化胞嘧啶免疫沉淀,发现大鼠CAMK2G启动子在分化的VSM中,损伤或细胞培养诱导的VSM Deffefe强化与Camk2G启动子甲基化并降低的表达。 我们首次报告该VSM细胞表型切换的第一次伴随着体内和培养的VSM合成表型细胞的受伤动脉中的胸腺嘧啶DNA糖基糖基酶(TDG)蛋白和mRNA表达的标记诱导。 沉默于VSM中的TDG促进了Camkiigamma和差异化标志物的表达,包括心肌素,并抑制VSM细胞增殖和损伤诱导的内部地段形成。 该研究表明,VSM中的CamkiiGamma表达受胞嘧啶甲基化/去甲基化的调节,并且TDG是该方法的重要决定因素,更广泛地,VSM表型切换和功能。

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