title: Vascular calcification is coupled with phenotypic conversion of vascular smooth muscle cells through Klf5-mediated transactivation of the Runx2 promoter.
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.
authors.affiliation: *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.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: *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.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: *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.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Zhou
authors.affiliation: *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.
authors.forename: Ruo-Nan
authors.initials: RN
authors.lastname: Zhang
authors.affiliation: *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.
authors.forename: Ming
authors.initials: M
authors.lastname: He
authors.affiliation: *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.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: *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.
authors.forename: Jin-Kun
authors.initials: JK
authors.lastname: Wen
mesh_terms: D000225:Adenine; D000818:Animals; D015153:Blotting, Western; D002114:Calcinosis / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D041681:NIH 3T3 Cells; D010641:Phenotype; D010710:Phosphates / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014511:Uremia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D061205:Vascular Calcification / Q000235:genetics* / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C492215:Klf5 protein, rat; D051741:Kruppel-Like Transcription Factors; D010710:Phosphates; C493717:Runx2 protein, rat; D000225:Adenine