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

1.Klotho促进脂肪细胞分化在小鼠3T3-L1细胞分化为脂肪细胞的过程中，Klotho的表达在早期显著增加。然后将Klotho-siRNA导入细胞进行Klotho抑制，并抑制脂肪细胞分化标志物PPAR-、CEBPα，β和δ。当Klotho质粒被导入后，脂肪细胞的分化被促进。加入纯化的Klotho蛋白后，脂肪细胞分化标志物也明显增加，油红0染色证实了这一点。这些结果表明，Klotho在早期促进脂肪细胞的分化(内分泌学，2006)2，Klotho抑制血管内皮细胞的炎症我们研究了Klotho的抗肿瘤坏死因子诱导的内皮细胞炎症的作用。当内皮细胞与肿瘤坏死因子-1共同孵育时，ICAM-1和VCAM-1等黏附分子的表达增加，核因子-B活性增强。Klotho蛋白可降低ICAM-1和VCAM-1的表达，降低NF-B的活性。I-B的磷酸化也受到抑制。Klotho和FGF23在脂肪细胞分化中的作用我们研究了与Klotho密切相关的FGF23的功能。当3T3-L1细胞分化为脂肪细胞时，Klotho的表达增加，而FGF23及其受体的表达降低。当脂肪细胞与Klotho蛋白孵育或不与Klotho蛋白孵育时，给予FGF23蛋白可抑制脂肪细胞的分化。FGF23在脂肪细胞分化中的作用不同于其他组织。

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.