Abstract
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.
Highlights
Vascular calcification is one of the major complications of atherosclerosis, diabetes mellitus, hypertension and chronic kidney disease
High Pi-induced Kruppel-like factor 5 (Klf5) expression and vascular smooth muscle cell (VSMC) calcification Previous studies have shown that the high Pi concentration induced VSMC calcification through increasing Runx2 expression [12]
The results showed that incubation with the high Pi medium for 6 days increased Klf5 and Runx2 mRNA expression by 1.0-fold and 1.76-fold, respectively
Summary
Vascular calcification is one of the major complications of atherosclerosis, diabetes mellitus, hypertension and chronic kidney disease. It decreases vessel elasticity and compliance of the vessel wall [1], leading to increased incidence of many cardiovascular diseases, such as myocardial infarction, hypertension and increased plaque rupture during angioplasty [2]. Many actors, including abnormal mineral metabolism, chronic inflammation, and oxidative stress, are associated with the generation of vascular calcification. Accumulating evidence indicates that vascular calcification is not due to passive precipitation of calcium Pi (phosphate), but rather is a tightly regulated process that resembles the ossification processes of the bone [3]. In response to high Pi stimulus, VSMCs increase expression a number of boneassociated proteins such as alkaline phosphatase, MGP, osteopontin and osteocalcin in vitro and in vivo [4,5], and decrease expression of VSMC differentiation marker genes, including SM (smooth muscle) α-actin and SM22α (smooth muscle 22α) [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
