2007 Fiscal Year Final Research Report Summary
The protective effect of Klotho protein from vascular senescence adipocyte differentiation and endothelial function
| Project/Area Number |
18590811
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
RAKUGI Hiromi Osaka University, Graduate School of Medicine, Professor (20252679)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Kazuhiko Osaka University, Hospital, Assistant Professor (60379245)
OHISHI Mitsuru Osaka University, Graduate School of Medicine, Assistant Professor (50335345)
OGIHARA Toshio Osaka University, Professor Emeritus (60107042)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Klotho / adipocyte differentiation / adhesion molecle / 3T3-L1 cells / endothelial cells |
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| Research Abstract |
1. Klotho promotes adipocyte differentiation
During the mouse 3T3-L1 cells were differentiated into adipocytes, Klotho expression greatly increased in the early stage. Then Klotho-siRNA was transfected into cells for klotho inhibition, and adipocyte differentiation markers, such as PPAR□, CEBPα, β and δ, were suppressed. When the Klotho plasmid was transfected, adipocyte differentiation was promoted. The adipocyte differentiation markers were also increased by administration of purified Klotho protein, and it was confirmed by Oil red 0 staining. These results suggested that Klotho promotes adipocyte differentiation in the early stage (Endocrinology, 2006).
2, Klotho suppresses inflammation in the vascular endothelial cells
We investigated the Klotho function against TNF-□ induced inflammation in the endothelial cells. When the endothelial cells were incubated with TNF-□, the expression of adhesion molecules, such as ICAM-1 and VCAM-1, was elevated and NF-□B activity was increased. The administration of Klotho protein reduced the expression of ICAM-1 and VCAM-1, and NF-□B activity. The phosphorylation of I□-B was also suppressed. These results showed that Klotho may suppress endothelial inflammation via NF- □B pathway.
3,Klotho and FGF23 function on the adipocyte differentiation
We investigated the function of FGF23 which closely correlated with Klotho. Klotho expression was increased, when 3T3-L1 cells were differentiated into adipocytes, on the contrary, FGF23 and the receptor expressions were decreased. FGF23 protein administration suppressed adipocyte differentiation, when the cells were incubated with or without Klotho protein. This function of FGF23 on the adipocyte differentiation differs from that in the other tissues.
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