Wei Jiang, Yu Yang, Luo Guang-Hua, Feng Yue-Hua, Shi Yuan-Ping, Zhang Jun, Mu Qin-Feng, Yu Miao-Mei, Pan Li-Li, Berggren-Söderlund Maria, Nilsson-Ehle Peter, Zhang Xiao-Ying, Xu Ning
Department of Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lunds University, S-221 85, Lund, Sweden.
Lipids Health Dis. 2017 Mar 31;16(1):66. doi: 10.1186/s12944-017-0458-x.
We have previously demonstrated that estrogen could significantly enhance expression of apolipoprotein M (apoM), whereas the molecular basis of its mechanism is not fully elucidated yet. To further investigate the mechanism behind the estrogen induced up-regulation of apoM expression.
Our results demonstrated either free 17β-estradiol (E2) or membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) could modulate human apoM gene expression via the estrogen receptor alpha (ER-α) pathway in the HepG2 cells. Moreover, experiments with the luciferase activity analysis of truncated apoM promoters could demonstrate that a regulatory region (from-1580 to -1575 bp (-GGTCA-)) upstream of the transcriptional start site of apoM gene was essential for the basal transcriptional activity that regulated by the ER-α. With the applications of an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay, we could successfully identify a specific ER-α binding element in the apoM promoter region.
In summary, the present study indicates that 17β-estradiol induced up-regulation of apoM in HepG2 cells is through an ER-α-dependent pathway involving ER-α binding element in the promoter of the apoM gene.
我们之前已经证明雌激素能够显著增强载脂蛋白M（apoM）的表达，但其机制的分子基础尚未完全阐明。为了进一步研究雌激素诱导apoM表达上调背后的机制。
我们的结果表明，游离的17β-雌二醇（E2）或膜不可渗透的牛血清白蛋白结合型E2（E2-BSA）均可通过雌激素受体α（ER-α）途径调节HepG2细胞中人apoM基因的表达。此外，对截短的apoM启动子进行荧光素酶活性分析的实验表明，apoM基因转录起始位点上游的一个调控区域（从-1580至-1575 bp（-GGTCA-））对于由ER-α调控的基础转录活性至关重要。通过电泳迁移率变动分析和染色质免疫沉淀分析的应用，我们成功地在apoM启动子区域鉴定出一个特异性的ER-α结合元件。
总之，本研究表明17β-雌二醇在HepG2细胞中诱导apoM上调是通过依赖ER-α的途径，该途径涉及apoM基因启动子中的ER-α结合元件。
