Hypoxia-induced TET1 facilitates trophoblast cell migration and invasion through HIF1α signaling pathway.
Hypoxia-induced TET1 facilitates trophoblast cell migration and invasion through HIF1α signaling pathway.
复制标题
缺氧诱导的 TET1 通过 HIF1α 信号通路促进滋养层细胞迁移和侵袭。
DOI：
10.1038/s41598-017-07560-7
复制
发表时间：
2017-08-14
影响因子：
4.6
通讯作者：
Duan T
中科院分区：
文献类型：
--
作者：
Zhu J;Wang K;Li T;Chen J;Xie D;Chang X;Yao J;Wu J;Zhou Q;Jia Y;Duan T
低氧是调节滋养层生物学功能（包括细胞迁移、侵袭和增殖）的典型外在因素。 10-11 易位甲基胞嘧啶双加氧酶 1 (TET1) 是一种将 5-甲基胞嘧啶 (5-mC) 转化为 5-羟甲基胞嘧啶 (5-hmC) 的酶，在癌细胞缺氧时转录被激活。因此，我们重点关注TET1在生理缺氧环境（3%氧）下对滋养层功能的作用，这与早期胎盘形成有关。在这里，我们发现与正常足月胎盘相比，TET1 在妊娠早期绒毛中高表达。体外实验中，3%氧气暴露后，JEG3细胞中TET1 mRNA和蛋白表达水平均增加，JEG3细胞的迁移和侵袭能力上调。此外，TET1敲低降低了暴露于3%氧气的JEG3细胞的迁移、侵袭和增殖，HIF1α及其下游靶基因的表达也降低，这与HIF1α启动子的高甲基化有关。最后，HIF1α蛋白表达的增加逆转了TET1敲低对暴露于3%氧气的JEG3细胞迁移和侵袭的抑制作用。这些数据表明，缺氧诱导的TET1表达通过HIF1α信号通路促进滋养层细胞迁移和侵袭，这在胎盘形成过程中发挥着重要作用。
Low oxygen is a typical extrinsic factor for the regulation of trophoblast biological function, including cell migration, invasion and proliferation. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1), an enzyme converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), is transcriptionally activated by hypoxia in cancer cells. Therefore, we focus on the role of TET1 on trophoblast function in a physiologically hypoxic environment (3% oxygen), which is related to early placentation. Here, we found that TET1 was highly expressed in first trimester villi compared with normal term placentas. In vitro, both TET1 mRNA and protein expression levels in JEG3 cells were increased following exposure to 3% oxygen, and the migration and invasion capacities of JEG3 cells were up-regulated. Furthermore, TET1 knockdown decreased the migration, invasion and proliferation of JEG3 cells exposed to 3% oxygen, and the expression of HIF1α and its downstream target genes was also decreased, which was related to hyper-methylation of the HIF1α promoter. Finally, increased HIF1α protein expression reversed the inhibitory effect of TET1 knockdown on the migration and invasion of JEG3 cells exposed to 3% oxygen. These data show that hypoxia-induced TET1 expression facilitates trophoblast cell migration and invasion through the HIF1α signaling pathway, which plays an important role during placentation.
登录
查看更多内容
影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
16
作者：
Piccolo, Francesco M.;Bagci, Hakan;Brown, Karen E.;Landeira, David;Soza-Ried, Jorge;Feytout, Amelie;Mooijman, Dylan;Hajkova, Petra;Leitch, Harry G.;Tada, Takashi;Kriaucionis, Skirmantas;Dawlaty, Meelad M.;Jaenisch, Rudolf;Merkenschlager, Matthias;Fisher, Amanda G.
通讯作者：
Fisher, Amanda G.
影响因子：
9.8
作者：
Koklanaris, N;Nwachukwu, JC;Lee, MJ
通讯作者：
Lee, MJ
影响因子：
8.8
作者：
Mariani CJ;Vasanthakumar A;Madzo J;Yesilkanal A;Bhagat T;Yu Y;Bhattacharyya S;Wenger RH;Cohn SL;Nanduri J;Verma A;Prabhakar NR;Godley LA
通讯作者：
Godley LA
影响因子：
3.6
作者：
Ietta, Francesca;Wu, Yuanhong;Caniggia, Isabella
通讯作者：
Caniggia, Isabella