J Cell Biochem:TIEG1在Lrp5/6介导的瓣膜成骨中上调

2018-10-13 MedSci MedSci原创

我们之前已经证明Lrp5/6/β-连环蛋白在瓣膜钙化中起重要作用,通过增加骨矿物质含量和增厚瓣膜来定义特定成骨表型。最近的研究表明,TIEG1可能参与调节骨中的Wnt信号通路,已知其在成骨细胞分化和骨矿化中起关键作用。因此,我们试图在已建立的高胆固醇血症性瓣膜病模型中测试TIEG1在介导Wnt信号传导中的作用。 我们以前的模型用胆固醇饮食治疗敲基因小鼠Lrp5-/-/ApoE -/ -小鼠与

我们之前已经证明Lrp5/6/β-连环蛋白在瓣膜钙化中起重要作用,通过增加骨矿物质含量和增厚瓣膜来定义特定成骨表型。最近的研究表明,TIEG1可能参与调节骨中的Wnt信号通路,已知其在成骨细胞分化和骨矿化中起关键作用。因此,我们试图在已建立的高胆固醇血症性瓣膜病模型中测试TIEG1在介导Wnt信号传导中的作用。

我们以前的模型用胆固醇饮食治疗敲基因小鼠Lrp5-/-/ApoE -/ -小鼠与野生型对照小鼠(n = 180)。组I(n = 60)正常饮食,组II(n = 60)0.25%胆固醇饮食(w/w),组III(n = 60)0.25%(w/w)胆固醇饮食+ atorv,进行基因测试TIEG1,Lrp6和Runx2的表达。实时聚合酶链反应证实,与Lrp6轻度增加的对照组相比,高胆固醇血症双敲除和单敲除瓣膜中TIEG1和Runx2的基因表达上调。

为了证实这一机制,体外瓣膜细胞中β-连环蛋白,TIEG1和LEF1的共表达导致TOPFLASH报告基因的共激活,通过转化生长因子-β处理刺激后TIEG1和β-连环蛋白在瓣膜间质细胞(VICs)的细胞核中彼此共定位的观察进一步证实了这一点。

总之,该研究结果表明TIEG1在介导瓣膜骨生成中发挥重要作用。

原始出处:

Rajamannan NM. TIEG1 is upregulated in Lrp5/6-mediated valve osteogenesis. J Cell Biochem. 2018 Sep 23. doi: 10.1002/jcb.27606.

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    2019-07-10 维他命
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    2019-09-01 sunylz
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    2018-10-15 zhaojie88
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