Kurosu Hiroshi, Kuro-O Makoto
Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Mol Cell Endocrinol. 2009 Feb 5;299(1):72-8. doi: 10.1016/j.mce.2008.10.052. Epub 2008 Nov 21.
The Klotho gene encodes a single-pass transmembrane protein and functions as an aging-suppressor gene, which extends lifespan when overexpressed and accelerates the development of aging-like phenotypes when disrupted in mice. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate and vitamin D homeostasis. It has been shown that Klotho-deficient mice and Fgf23 knockout mice exhibit identical phenotypes. This observation led to the identification of Klotho as a cofactor essential for interactions between FGF23 and FGF receptors. In addition to the Klotho-FGF23 axis, recent studies has shown that betaKlotho, a Klotho family protein, also functions as a cofactor required for FGF19 and FGF21 signaling and determines the tissue-specific metabolic activities of FGF19 and FGF21. This review summarizes recent progress in understanding of Klotho and betaKlotho function in the regulation of tissue-specific metabolic activity of the endocrine fibroblast growth factors (FGF19, FGF21, and FGF23).
Klotho基因编码一种单次跨膜蛋白，作为一种衰老抑制基因发挥作用，在小鼠中过表达时可延长寿命，而在基因被破坏时会加速衰老样表型的发展。成纤维细胞生长因子23（FGF23）是一种骨源性激素，可调节磷酸盐和维生素D的稳态。研究表明，Klotho基因缺陷小鼠和Fgf23基因敲除小鼠表现出相同的表型。这一观察结果使得Klotho被确定为FGF23与FGF受体相互作用所必需的辅助因子。除了Klotho-FGF23轴，最近的研究表明，βKlotho是一种Klotho家族蛋白，它也作为FGF19和FGF21信号传导所需的辅助因子，并决定FGF19和FGF21的组织特异性代谢活性。本综述总结了在理解Klotho和βKlotho在调节内分泌成纤维细胞生长因子（FGF19、FGF21和FGF23）的组织特异性代谢活性方面的最新进展。
