Fibroblast growth factor 23, klotho and heparin.
Fibroblast growth factor 23, klotho and heparin.
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DOI：
10.1097/mnh.0000000000000895
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发表时间：
2023-07-01
影响因子：
3.2
通讯作者：
Faul, Christian
中科院分区：
文献类型：
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作者：
Thomas, S. Madison;Li, Qing;Faul, Christian
成纤维细胞生长因子（FGF） 23是一种骨源性激素，通过靶向肾脏调节磷酸盐和维生素D代谢。当FGF23在慢性肾脏疾病（CKD）中高度升高时，FGF23也可以靶向心脏并诱导病理性重构。在这里，我们讨论了FGF23的生理和病理作用的机制，重点是它的FGF受体（FGFR）和共受体。Klotho是一种跨膜蛋白，在生理靶细胞上作为FGF23的FGFR共受体。Klotho也作为循环变体存在，最近的研究表明可溶性Klotho （sKL）可以在不表达Klotho的细胞中介导FGF23的作用。此外，人们认为FGF23的作用不需要硫酸肝素（HS），一种作为其他FGF亚型共受体的蛋白聚糖。然而，最近的研究表明，HS可能是FGF23:FGFR信号复合物的一部分，并调节FGF23诱导的效应。sKL和HS作为循环中调节FGF23作用的FGFR共受体出现。实验研究表明，sKL可预防ckd相关的心脏损伤，而HS可加速ckd相关的心脏损伤。然而，这些发现的体内相关性仍然是推测性的。
Fibroblast growth factor (FGF) 23 is a bone-derived hormone that regulates phosphate and vitamin D metabolism by targeting the kidney. When highly elevated, such as in chronic kidney disease (CKD), FGF23 can also target the heart and induce pathologic remodeling. Here we discuss the mechanisms that underlie the physiologic and pathologic actions of FGF23, with focus on its FGF receptors (FGFR) and co-receptors. Klotho is a transmembrane protein that acts as an FGFR co-receptor for FGF23 on physiologic target cells. Klotho also exists as a circulating variant, and recent studies suggested that soluble klotho (sKL) can mediate FGF23 effects in cells that do not express klotho. Furthermore, it has been assumed that the actions of FGF23 do not require heparan sulfate (HS), a proteoglycan that acts as a co-receptor for other FGF isoforms. However, recent studies revealed that HS can be part of the FGF23:FGFR signaling complex and modulate FGF23-induced effects. sKL and HS have appeared as circulating FGFR co-receptors that modulate the actions of FGF23. Experimental studies suggest that sKL protects from and HS accelerates CKD-associated heart injury. However, the in vivo relevance of these findings is still speculative.
DOI：
10.1083/jcb.200106075
发表时间：
2001-11-26
期刊：
The Journal of cell biology
影响因子：
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作者：
Allen BL;Filla MS;Rapraeger AC
通讯作者：
Rapraeger AC