Li Yuan-Yuan, Hao Tong, Lu Yun, Liu Yue-Hua
Department of Orthodontics, Shanghai Stomatological Disease Center; Oral Biomedical and Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University. Shanghai 200031, China. E-mail:
Shanghai Kou Qiang Yi Xue. 2018 Aug;27(4):354-359.
To investigate the role of 17β-estradiol (E2) and resveratrol dimer (RD) on HIF-1α and the underlying mechanism.
Mice genioglossus myoblasts were isolated and cultured, and the estrogen receptor-α (ERα) shRNA lentivirus was used for gene knockdown. Cells in different groups were treated with different agents (E2, or RD, or E2 and LY294002), then incubated in normoxia or hypoxia for 24 h, the expressions of HIF-1α, ERα, ERβ, total-Akt and phospho-Akt were detected using qRT-PCR and Western blot. Statistical analysis was completed with SPSS 17.0 software package.
Both E2 and RD inhibited the overexpression of HIF-1α induced by hypoxia at mRNA and protein levels, and these effects were eliminated by genetic silencing of ERα by RNAi. Mechanically, E2 activated PI3K/Akt pathways to induce HIF-1α expression.
ERα may be responsible for down-regulation of HIF-1α by E2 or RD via activation of downstream PI3K/Akt pathways.
探讨17β-雌二醇（E2）和白藜芦醇二聚体（RD）对缺氧诱导因子-1α（HIF-1α）的作用及其潜在机制。
分离培养小鼠颏舌肌成肌细胞，利用雌激素受体-α（ERα）短发夹RNA慢病毒进行基因敲低。不同组别的细胞用不同试剂（E2、RD或E2与LY294002）处理，然后在常氧或缺氧条件下孵育24小时，采用实时定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测HIF-1α、ERα、ERβ、总蛋白激酶B（total-Akt）和磷酸化蛋白激酶B（phospho-Akt）的表达。使用SPSS 17.0软件包进行统计分析。
E2和RD在mRNA和蛋白质水平均抑制缺氧诱导的HIF-1α过表达，RNA干扰介导的ERα基因沉默消除了这些作用。机制上，E2激活磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）信号通路诱导HIF-1α表达。
ERα可能通过激活下游PI3K/Akt信号通路介导E2或RD对HIF-1α的下调作用。
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