Flufenamic Acid Inhibits Adipogenic Differentiation of Mesenchymal Stem Cells by Antagonizing the PI3K/AKT Signaling Pathway
Flufenamic Acid Inhibits Adipogenic Differentiation of Mesenchymal Stem Cells by Antagonizing the PI3K/AKT Signaling Pathway
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DOI：
10.1155/2020/1540905
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发表时间：
2020-03-16
影响因子：
4.3
通讯作者：
Zhou, Yongsheng
中科院分区：
文献类型：
--
作者：
Liu, Xuenan;Zheng, Li;Zhou, Yongsheng
目标.氟芬那酸（FFA）是芬那酸类的代表化合物，是一类重要的非甾体抗炎药。本研究旨在观察游离脂肪酸对人骨髓间充质干细胞（MSCs）成脂的影响，并探讨其可能的作用机制。方法.为探讨游离脂肪酸（FFA）对人骨髓间充质干细胞（hMSCs）成脂分化的影响，以人脂肪源性干细胞（hASCs）和人骨髓间充质干细胞（hBMMSCs）为代表，在体外脂肪分化过程中加入FFA。在裸鼠以及卵巢切除（OVX）和老年小鼠中，使用异位脂肪形成测定来评价FFA在体内的作用。为探讨FFA的作用机制，采用Western blot方法检测FFA对PI 3 K/AKT信号通路的激活作用。结果我们的研究结果表明，在一定浓度下，FFA在体外和体内均抑制人MSC的脂肪形成。FFA通过抑制PI 3 K/AKT通路抑制人MSC的脂肪形成。结论.本研究表明，游离脂肪酸可用于组织工程和与骨髓间充质干细胞过度成脂分化相关的疾病中抑制人骨髓间充质干细胞的成脂。
Objectives. Flufenamic acid (FFA) is a representative of the fenamic acids, an important group of NSAIDs. In the present study, we study the effects of FFA on adipogenesis of human mesenchymal stem cells (MSCs) and we explore the potential mechanism. Methods. To investigate the effects of FFA on adipogenic differentiation of hMSCs, human adipose-derived stem cells (hASCs) and human bone marrow mesenchymal stem cells (hBMMSCs), representative of hMSCs, were treated with FFA during adipogenic differentiation in vitro. The effects of FFA in vivo were evaluated using a heterotopic adipose formation assay in nude mice as well as ovariectomized (OVX) and aged mice. To explore the mechanism of FFA, Western blot was used to determine activation of the PI3K/AKT signaling pathway. Results. Our results demonstrate that, at certain concentrations, FFA inhibited adipogenesis of human MSCs both in vitro and in vivo. Mechanistically, FFA inhibited adipogenesis of human MSCs by inhibiting the PI3K/AKT pathway. Conclusions. The present study indicated that FFA could be used to inhibit adipogenesis of human MSCs in tissue engineering and diseases related to excessive adipogenic differentiation of MSCs.