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The protective effect of Klotho protein from vascular senescence adipocyte differentiation and endothelial function

Klotho蛋白对血管衰老脂肪细胞分化及内皮功能的保护作用

基本信息

批准号：
18590811
负责人：
RAKUGI Hiromi
金额：
$ 2.49万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590811/
关键词：
Klotho adipocyte differentiation adhesion molecle 3T3-L1 cells endothelial cells klotho siRNA

项目摘要

1. Klotho promotes adipocyte differentiationDuring 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 cellsWe 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 differentiationWe 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.

1. Klotho促进脂肪细胞分化在小鼠3 T3-L1细胞向脂肪细胞分化的过程中，Klotho的表达在早期显著增加。然后将Klotho-siRNA转染入细胞中以抑制Klotho，并且抑制脂肪细胞分化标志物，如PPAR□、CEBPα、β和δ。当Klotho质粒被转染时，脂肪细胞分化被促进。脂肪细胞分化标志物也通过施用纯化的Klotho蛋白而增加，并且通过油红0染色证实。这些结果表明Klotho在早期促进脂肪细胞分化（Endocrinology，2006）。2、Klotho抑制血管内皮细胞的炎症我们研究了Klotho对TNF-α诱导的内皮细胞炎症的作用。当内皮细胞与TNF-□共同孵育时，粘附分子如ICAM-1和VCAM-1的表达增加，NF-□B活性增加。Klotho蛋白的施用降低了ICAM-1和VCAM-1的表达以及NF-B活性。I□-B的磷酸化也受到抑制。这些结果表明Klotho可能通过NF- □B途径抑制内皮炎症。3、Klotho和FGF 23对脂肪细胞分化的作用我们研究了与Klotho密切相关的FGF 23的功能。3 T3-L1细胞分化为脂肪细胞后，Klotho表达增加，而FGF 23及其受体表达下降。当细胞与Klotho蛋白一起或不与Klotho蛋白一起孵育时，FGF 23蛋白施用抑制脂肪细胞分化。FGF 23在脂肪细胞分化中的这种功能不同于在其他组织中的功能。