Roles of FGFs As Paracrine or Endocrine Signals in Liver Development, Health, and Disease.
Roles of FGFs As Paracrine or Endocrine Signals in Liver Development, Health, and Disease.
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DOI：
10.3389/fcell.2016.00030
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发表时间：
2016
影响因子：
5.5
通讯作者：
Konishi M
中科院分区：
文献类型：
--
作者：
Itoh N;Nakayama Y;Konishi M
肝脏在新陈代谢、免疫系统和解毒等多个过程中发挥着重要作用，并且还具有独特的再生能力。 FGF 是在发育、健康和疾病中具有多种功能的生长因子。 FGF家族现在有22名成员。多种 FGF 已被证明在肝脏发育、健康和疾病中发挥旁分泌信号的作用。 FGF8和FGF10参与胚胎肝脏发育，FGF7和FGF9参与肝损伤修复，FGF5、FGF8、FGF9、FGF17和FGF18参与肝细胞癌的发生和进展。相比之下，FGF15/19和FGF21是内分泌信号。 FGF15/19 在回肠中产生，是胆汁酸代谢的负调节剂和胆囊充盈的刺激剂。 FGF15/19 是一种餐后、不依赖胰岛素的肝蛋白和糖原合成激活剂。它也是肝细胞癌和肝再生所必需的。 FGF21 是肝脏产生的肝因子。 FGF21 调节白色脂肪组织中的葡萄糖和脂质代谢。非酒精性脂肪肝患者血清 FGF21 水平升高。 FGF21 还可以预防非酒精性脂肪肝。这些发现为 FGF 在肝脏中的作用和肝病的潜在治疗策略提供了新的见解。
The liver plays important roles in multiple processes including metabolism, the immune system, and detoxification and also has a unique capacity for regeneration. FGFs are growth factors that have diverse functions in development, health, and disease. The FGF family now comprises 22 members. Several FGFs have been shown to play roles as paracrine signals in liver development, health, and disease. FGF8 and FGF10 are involved in embryonic liver development, FGF7 and FGF9 in repair in response to liver injury, and FGF5, FGF8, FGF9, FGF17, and FGF18 in the development and progression of hepatocellular carcinoma. In contrast, FGF15/19 and FGF21 are endocrine signals. FGF15/19, which is produced in the ileum, is a negative regulator of bile acid metabolism and a stimulator of gallbladder filling. FGF15/19 is a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. It is also required for hepatocellular carcinoma and liver regeneration. FGF21 is a hepatokine produced in the liver. FGF21 regulates glucose and lipid metabolism in white adipose tissue. Serum FGF21 levels are elevated in non-alcoholic fatty liver. FGF21 also protects against non-alcoholic fatty liver. These findings provide new insights into the roles of FGFs in the liver and potential therapeutic strategies for hepatic disorders.