Fibroblast growth factor-5 participates in the progression of hepatic fibrosis.
Fibroblast growth factor-5 participates in the progression of hepatic fibrosis.
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DOI：
10.1538/expanim.63.85
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发表时间：
2014
影响因子：
2.4
通讯作者：
Imaki J
中科院分区：
文献类型：
--
作者：
Hanaka H;Hamada T;Ito M;Nakashima H;Tomita K;Seki S;Kobayashi Y;Imaki J
非酒精性脂肪性肝炎 (NASH) 的特点是存在脂肪变性、炎症和纤维化，并且被认为是通过“二次打击过程”发展的；然而，其病理生理学仍不清楚。成纤维细胞生长因子（FGF）是肝素结合多肽，在许多发育和代谢过程中具有多种生物活性。特别是，FGF5 与高血压有关。我们使用自发性 Fgf5 缺失小鼠研究了 FGF5 的体内功能，并探讨了饮食在 NASH 发展中的作用。喂食高脂肪饮食的小鼠体重几乎没有增加，并且血清丙氨酸转氨酶、天冬氨酸转氨酶和非高密度脂蛋白胆固醇水平较高。肝脏组织学显示有明显的炎症、局灶性坏死、脂肪沉积和纤维化，与NASH的特征相似。 FGF5和高脂肪饮食在肝纤维化的病理生理学中发挥重要作用，Fgf5缺失小鼠可能为肝纤维化或NASH提供合适的模型。
Non-alcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation, and fibrosis and is believed to develop via a “two-hit process”; however, its pathophysiology remains unclear. Fibroblast growth factors (FGFs) are heparin-binding polypeptides with diverse biological activities in many developmental and metabolic processes. In particular, FGF5 is associated with high blood pressure. We investigated the function of FGF5 in vivo using spontaneously Fgf5 null mice and explored the role of diet in the development of NASH. Mice fed a high-fat diet gained little weight and had higher serum alanine transaminase, aspartate amino transferase, and non–high-density lipoprotein-cholesterol levels. Liver histology indicated marked inflammation, focal necrosis, fat deposition, and fibrosis, similar to the characteristics of NASH. FGF5 and a high-fat diet play significant roles in the pathophysiology of hepatic fibrosis and Fgf5 null mice may provide a suitable model for liver fibrosis or NASH.