Hormone-like (endocrine) Fgfs: their evolutionary history and roles in development, metabolism, and disease.
Hormone-like (endocrine) Fgfs: their evolutionary history and roles in development, metabolism, and disease.
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DOI：
10.1007/s00441-010-1024-2
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发表时间：
2010-10
影响因子：
3.6
通讯作者：
Itoh, Nobuyuki
中科院分区：
文献类型：
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作者：
Itoh, Nobuyuki
成纤维细胞生长因子（Fgfs）是一种在发育、修复和代谢中具有多种功能的蛋白质。人类Fgf基因家族共有22个成员，可分为三类：典型Fgf基因、细胞内Fgf基因和激素样Fgf基因。与在无脊椎动物和脊椎动物中发现的典型和细胞内Fgfs相反，激素样Fgfs， Fgf15/19， Fgf21和Fgf23是脊椎动物特异性的。激素样Fgfs的祖先基因是在脊椎动物进化早期由典型Fgfs的祖先基因通过基因复制而产生的。随后，Fgf15/19、Fgf21和Fgf23通过基因组复制事件从祖先基因中产生。典型的Fgfs以Fgf受体（Fgfr）依赖的方式作为自分泌/旁分泌因子。相反，激素样Fgfs以依赖fgfr的方式作为内分泌因子。典型的Fgfs具有肝素结合位点，这是Fgfs稳定结合和局部信号传递所必需的。相反，激素样Fgfs在进化过程中通过降低其肝素结合亲和力获得内分泌功能。Fgf15/19和Fgf23分别需要βKlotho和αKlotho作为辅因子。然而，Fgf21在生理上可能两者都不需要。激素样Fgfs在出生后的代谢中发挥作用，尽管它们也在胚胎阶段的发育中发挥作用。Fgf15/19调节肝脏胆汁酸代谢。Fgf21调节白色脂肪组织的脂质代谢。Fgf23调节血清磷酸盐和活性维生素D水平。遗传疾病或肿瘤引起的Fgf23信号紊乱导致代谢紊乱。此外，血清Fgf19或Fgf21水平因代谢紊乱而显著升高。激素样Fgfs是新兴的，在进化和功能上都很独特。
Fibroblast growth factors (Fgfs) are proteins with diverse functions in development, repair, and metabolism. The human Fgf gene family with 22 members can be classified into three groups, canonical, intracellular, and hormone-like Fgf genes. In contrast to canonical and intracellular Fgfs identified in invertebrates and vertebrates, hormone-like Fgfs, Fgf15/19, Fgf21, and Fgf23, are vertebrate-specific. The ancestral gene of hormone-like Fgfs was generated from the ancestral gene of canonical Fgfs by gene duplication early in vertebrate evolution. Later, Fgf15/19, Fgf21, and Fgf23 were generated from the ancestral gene by genome duplication events. Canonical Fgfs act as autocrine/paracrine factors in an Fgf receptor (Fgfr)-dependent manner. In contrast, hormone-like Fgfs act as endocrine factors in an Fgfr-dependent manner. Canonical Fgfs have a heparin-binding site necessary for the stable binding of Fgfrs and local signaling. In contrast, hormone-like Fgfs acquired endocrine functions by reducing their heparin-binding affinity during their evolution. Fgf15/19 and Fgf23 require βKlotho and αKlotho as cofactors, respectively. However, Fgf21 might physiologically require neither. Hormone-like Fgfs play roles in metabolism at postnatal stages, although they also play roles in development at embryonic stages. Fgf15/19 regulates bile acid metabolism in the liver. Fgf21 regulates lipid metabolism in the white adipose tissue. Fgf23 regulates serum phosphate and active vitamin D levels. Fgf23 signaling disorders caused by hereditary diseases or tumors result in metabolic disorders. In addition, serum Fgf19 or Fgf21 levels are significantly increased by metabolic disorders. Hormone-like Fgfs are newly emerging and quite unique in their evolution and function.
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影响因子：
1.8
作者：
Chen, W. -W.;Li, L.;Boden, G.
通讯作者：
Boden, G.
影响因子：
2
作者：
Itoh, Nobuyuki;Konishi, Morichika
通讯作者：
Konishi, Morichika
影响因子：
29.4
作者：
Johnson, Charis L.;Weston, Jacqueline Y.;Pin, Christopher L.
通讯作者：
Pin, Christopher L.
影响因子：
5.3
作者：
Goetz, Regina;Beenken, Andrew;Mohammadi, Moosa
通讯作者：
Mohammadi, Moosa
DOI：
10.1038/nrd2792
发表时间：
2009-03
期刊：
Nature reviews. Drug discovery
影响因子：
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作者：
通讯作者：
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