Vascular calcification is coupled with phenotypic conversion of vascular smooth muscle cells through Klf5-mediated transactivation of the Runx2 promoter.
Vascular calcification is coupled with phenotypic conversion of vascular smooth muscle cells through Klf5-mediated transactivation of the Runx2 promoter.
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通过 Klf5 介导的 Runx2 启动子反式激活，血管钙化与血管平滑肌细胞的表型转变相结合。
DOI：
10.1042/bsr20140103
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发表时间：
2014-11-04
影响因子：
4
通讯作者：
Wen JK
中科院分区：
文献类型：
--
作者：
Zhang J;Zheng B;Zhou PP;Zhang RN;He M;Yang Z;Wen JK
Klf 5（Krüppel样因子5）和Runx 2都参与VSMC（血管平滑肌细胞）的表型转换。然而，Klf 5和Runx 2在介导血管钙化中的潜在联系仍不清楚。本研究的目的是阐明Klf 5和Runx 2在介导VSMC钙化中的实际关系。我们发现，高Pi（磷酸盐）增加Klf 5的表达，这伴随着SM α-肌动蛋白和SM 22 α（平滑肌22 α）的损失，以及Runx 2表达的增加。Klf 5的过表达增加，而Klf 5的敲低减少，Runx 2表达和钙化。进一步的研究表明Klf 5直接与Runx 2启动子结合并激活其转录。在腺嘌呤诱导的尿毒症大鼠的钙化主动脉中，Klf 5也被显著诱导。总之，我们证明Klf 5介导的Runx 2诱导在高Pi诱导的VSMC钙化中起关键作用。高磷诱导Klf 5表达和VSMC钙化。Klf 5直接与Runx 2启动子结合并激活其转录。通过Klf 5介导的Runx 2启动子的反式激活，血管钙化与VSMC的表型转化相结合。
Both Klf5 (Krüppel-like factor 5) and Runx2 are involved in phenotypic switching of VSMC (vascular smooth muscle cells). However, the potential link between Klf5 and Runx2 in mediating vascular calcification remains unclear. The aim of the present study was to elucidate the actual relationship between Klf5 and Runx2 in mediating VSMC calcification. We found that high Pi (phosphate) increased the expression of Klf5, which is accompanied by loss of SM α-actin and SM22α (smooth muscle 22 α), as well as gain of Runx2 expression. Overexpression of Klf5 increased, while knockdown of Klf5 decreased, Runx2 expression and calcification. Further study showed that Klf5 bound directly to the Runx2 promoter and activated its transcription. Klf5 was also induced markedly in the calcified aorta of adenine-induced uremic rats. In conclusion, we demonstrate a critical role for Klf5-mediated induction of Runx2 in high Pi -induced VSMC calcification. High phosphate induces the expression of Klf5 and VSMC calcification. Klf5 binds directly to the Runx2 promoter and activates its transcription. Vascular calcification is coupled with phenotype conversion of VSMCs through Klf5-mediated transactivation of Runx2 promoter.