Vascular calcification is coupled with phenotypic conversion of vascular smooth muscle cells through Klf5-mediated transactivation of the Runx2 promoter

Bioscience Reports

Pei‑pei Zhou¹  Zhan Yang¹  Bin Zheng¹  Jin‑Kun Wen¹  Ming He¹  Ruo‑Nan Zhang¹ 

[1] Department of Biochemistry and Molecular Biology, the Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, No. 361, Zhongshan East Road, Shijiazhuang 050017, China;

关键词: high phosphate;    Klf5;    Runx2;    vascular calcification;    vascular smooth muscle cell (VSMC);   

DOI  :  10.1042/BSR20140103

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown