The studies on the roles of transcriptional factors in pathogenesis of vascular calcification by chronic kidney disease and their application for the therapy

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To reveal the mechanisms which induce vascular calcification in the patients with chronic kidney disease, roles of transcriptional factors which are related to vascular calcification are studied in the present study. We found that Klf4, a transcriptional factor, plays important roles in transformation of vascular smooth muscle cells to osteocyte-like cells by hyperphosphathemia in the in vivo and in vitro experiments. It was also shown that by the same experimental system hyperglycemia is not a significant factor for worsening of vascular calcification. In addition, by vascular smooth muscle cell specific inactivation of NF-kB activity in mouse, endothelial thickening arteriosclerosis by vascular injury was ameliorated. Currently, we are examining the roles of NF-kB in the pathogenesis of vascular calcification by chronic renal failure, using these genetically modified mouse.