Biphasic effects of FGF2 on adipogenesis.

Biphasic effects of FGF2 on adipogenesis.
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DOI:
10.1371/journal.pone.0120073
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Lee DK
Lee DK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kim S;Ahn C;Bong N;Choe S;Lee DK

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尽管据报道来自缺乏 FGF2 的小鼠的干细胞显示出增强的脂肪生成能力,但迄今为止使用体外细胞培养系统的文献报道了关于 FGF2 在脂肪生成中的作用的相互矛盾的结果。我们在这里证明,根据浓度,FGF2 可以通过调节 ERK 信号通路的激活,作为体外脂肪生成的正因子或负因子。浓度低于 2 ng/ml 的 FGF2 可增强人脂肪干细胞 (hASC) 的体外脂肪生成。然而,浓度高于 10 ng/ml 的 FGF2 能够通过维持 ERK 的持续磷酸化来抑制脂肪生成,并作为 BMP 配体的显性负性脂肪生成因子发挥作用。高脂饮食诱导的肥胖C57BL/6小鼠脂肪组织中FGF2的表达水平低于正常饮食小鼠,表明脂肪组织中FGF2的表达水平可能与脂肪组织的大小呈负相关。我们观察到 FGF2 对脂肪生成的浓度依赖性双相效应以及显性负效应,为理解 FGF2 在脂肪生成和脂肪组织发育中的作用提供了机制基础。
Although stem cells from mice deficient of FGF2 have been reported to display enhanced capacity for adipogenesis, the literature using in vitro cell culture system has so far reported conflicting results on the role of FGF2 in adipogenesis. We here demonstrate that FGF2, depending on concentration, can function as either a positive or negative factor of in vitro adipogenesis by regulating activation of the ERK signaling pathway. FGF2 at concentrations lower than 2 ng/ml enhanced in vitro adipogenesis of human adipose-derived stem cells (hASCs). However, FGF2 at concentrations higher than 10 ng/ml was able to suppress adipogenesis by maintaining sustained phosphorylation of ERK and function as a dominant negative adipogenic factor toward BMP ligands. Expression levels of FGF2 in the fat tissues from high fat diet induced obese C57BL/6 mice were lower than those from normal chow diet mice, indicating that expression levels of FGF2 in the fat tissues might be in reverse correlation with the size of fat tissues. Our observation of concentration dependent biphasic effect as well as dominant negative effect of FGF2 on adipogenesis provides a mechanistic basis to understand roles of FGF2 in adipogenesis and development of fat tissues.
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