Inhibition of adipocyte differentiation by phytoestrogen genistein through a potential downregulation of extracellular signal-regulated kinases 1/2 activity.
Inhibition of adipocyte differentiation by phytoestrogen genistein through a potential downregulation of extracellular signal-regulated kinases 1/2 activity.
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DOI：
10.1002/jcb.21753
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发表时间：
2008-08-01
影响因子：
4
通讯作者：
Xiao, Zhou-Sheng
中科院分区：
文献类型：
--
作者：
Liao, Qing-Chuan;Li, Ya-Lin;Qin, Yan-Fang;Quarles, L. Darryl;Xu, Kang-Kang;Li, Rong;Zhou, Hong-Hao;Xiao, Zhou-Sheng
关键词：
本研究旨在探讨染料木黄酮对小鼠骨髓间充质干细胞（BMSC）成脂分化的影响及其可能的信号通路。Western blotting分析成脂特异性蛋白如PPARγ、C/EBPα、aP 2和脂肪细胞的形成来评估终末成脂分化。用成脂混合物处理小鼠BMSC培养物导致细胞外信号调节激酶1和2（ERK 1/2）在成脂早期（从第3天至第9天）持续活化，ERK 1/2是促分裂原活化蛋白激酶（MAPK）家族的成员。特异性MEK抑制剂PD 98059抑制ERK 1/2活化可逆转诱导的成脂分化。染料木黄酮剂量依赖性地降低小鼠BMSC培养物中ERK 1/2的磷酸化。染料木黄酮孵育的整个培养期间，以及在早期阶段的培养期间，应用显着抑制小鼠骨髓基质细胞培养物的成脂分化。而金雀异黄素在后期（第9天后）孵育，没有观察到对脂肪形成分化的抑制作用。在存在成纤维细胞生长因子-2（FGF-2）（ERK 1/2信号通路的激活剂）的情况下用染料木黄酮处理的BMSC培养物表达正常水平的ERK 1/2活性，并且在这样做时能够经历脂肪形成。我们的研究结果表明，ERK 1/2信号通路在脂肪形成的早期阶段（从第3天至第9天）的激活是必不可少的成脂分化的BMSC培养物，和染料木素抑制成脂分化通过潜在的下调ERK 1/2活性在这个早期阶段的脂肪形成。
In the current study, we investigated the effects of genistein on adipogenic differentiation of mouse bone marrow-derived mesenchymal stem cell (BMSC) cultures and its potential signaling pathway. The terminal adipogenic differentiation was assessed by western-blotting analysis of adipogenic-specific proteins such as PPARγ, C/EBPα, and aP2 and the formation of adipocytes. Treatment of mouse BMSC cultures with adipogenic cocktail resulted in sustained activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), which are members of the mitogen-activated protein kinase (MAPK) family, at the early phase of adipogenesis (from days 3 to 9). Inhibition of ERK1/2 activation by PD98059, a specific MEK inhibitor, reversed the induced adipogenic differentiation. Genistein dose-dependently decreased the phosphorylation of ERK1/2 in mouse BMSC cultures. Genistein incubation for the entire culture period, as well as that applied during the early phase of the culture period, significantly inhibited the adipogenic differentiation of mouse BMSC cultures. While genistein was incubated at the late stage (after day 9), no inhibitory effect on adipogenic differentiation was observed. BMSC cultures treated with genistein in the presence of fibroblast growth factor-2 (FGF-2), an activator of the ERK1/2 signaling pathway, expressed normal levels of ERK1/2 activity, and, in so doing, are capable of undergoing adipogenesis. Our results suggest that activation of the ERK1/2 signaling pathway during the early phase of adipogenesis (from days 3 to 9) is essential to adipogenic differentiation of BMSC cultures, and that genistein inhibits the adipogenic differentiation through a potential downregulation of ERK1/2 activity at this early phase of adipogenesis.
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影响因子：
4.1
作者：
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通讯作者：
Binétruy, B
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