Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2012: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
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Outline of Final Research Achievements |
Both clinical and basic research demonstrated conflicting evidence regarding the pathophysiological role of Fibroblast growth factor 23 (FGF23) concentration in vascular calcification. We determine the effects of FGF23 on the osteoblastic gene expression in vascular smooth muscle cells (VSMC). HASMC transduced with adenovirus expressing human FGF23 (Ad-FGF23) exhibited a significant decrease in the expression of the osteoblast-marker genes. Of note, Ad-FGF23 increased mRNA and protein levels for osteoprotegerin (OPG), and human OPG promoter was activated by FGF23. FGF23 up-regulated OPG expression, whereas depletion of Klotho by siRNA attenuated FGF23-induced OPG expression. These results indicate that FGF23 suppresses osteoblastic gene expression and induces OPG expression in HASMC, and support the hypothesis that FGF23 counteracts the osteogenic conversion of vascular SMC as a component of compensatory mechanisms to mitigate the vascular calcification.
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