Nagai R, Saito Y, Ohyama Y, Aizawa H, Suga T, Nakamura T, Kurabayashi M, Kuroo M
Second Department of Internal Medicine, Gunma University School of Medicine, Japan.
Cell Mol Life Sci. 2000 May;57(5):738-46. doi: 10.1007/s000180050038.
The human aging process is associated with vascular endothelial dysfunction. However, humoral factors which might protect against endothelial dysfunction during aging have not yet been identified. We recently identified the klotho gene as a possible regulator of human aging. In the present study using the klotho-deficient heterozygous mouse, we examined whether the Klotho protein is a humoral factor protecting against endothelial dysfunction. We further cloned rat klotho cDNA and investigated whether klotho mRNA expression in rat kidney is altered under pathological conditions such as hypertension, hyperlipidemia, renal failure, and inflammatory stress. The Klotho protein itself, or its metabolites, promotes endothelial NO production in aorta as well as arterioles, and klotho mRNA in kidney is downregulated under sustained circulatory stress.
人类衰老过程与血管内皮功能障碍相关。然而，尚未确定在衰老过程中可能预防内皮功能障碍的体液因子。我们最近将klotho基因鉴定为人类衰老的一种可能调节因子。在本研究中，我们使用klotho基因缺陷的杂合小鼠，研究Klotho蛋白是否是预防内皮功能障碍的体液因子。我们进一步克隆了大鼠klotho cDNA，并研究了在高血压、高脂血症、肾衰竭和炎症应激等病理条件下大鼠肾脏中klotho mRNA表达是否发生改变。Klotho蛋白本身或其代谢产物可促进主动脉和小动脉中内皮一氧化氮的生成，并且在持续循环应激下肾脏中的klotho mRNA会下调。
