Upregulation of Indian hedgehog gene in the uterine epithelium by leukemia inhibitory factor during mouse implantation.
Upregulation of Indian hedgehog gene in the uterine epithelium by leukemia inhibitory factor during mouse implantation.
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DOI：
10.1262/jrd.19120
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发表时间：
2008-01
期刊：
影响因子：
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通讯作者：
Shoichi Wakitani;E. Hondo;Thanmaporn Phichitraslip;C. Stewart;Y. Kiso
中科院分区：
文献类型：
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作者：
Shoichi Wakitani;E. Hondo;Thanmaporn Phichitraslip;C. Stewart;Y. Kiso
白血病抑制因子（LIF）和印度刺猬（Ihh）是小鼠胚胎着床所必需的，分别受17 β-雌二醇（E2）和孕酮的调节。本研究采用DNA微阵列技术研究了LIF对着床期子宫腔上皮中Ihh和Ihh相关因子的影响。野生型小鼠Ihh mRNA表达在妊娠第4天达到高峰，孕激素受体（Pgr）mRNA表达在妊娠第5天下降。另一方面，在LIF-/-小鼠中未观察到这些表达变化。在延迟着床的小鼠中，注射LIF上调Ihh和Pgr mRNA。这种Pgr的上调是短暂的，并且先于Ihh mRNA的增加。在LIF-/-基因型的延迟着床小鼠中，注射E2后Ihh mRNA也增加。E2不影响延迟着床LIF-/-小鼠子宫腔上皮Pgr mRNA的转录。使用针对Ihh的C-末端表位的抗体，通过蛋白质印迹分析检测通过Ihh的自身蛋白水解切割的未加工的Ihh蛋白，但不检测C-末端肽。在植入期间，未处理的Ihh未显示野生型和LIF-/-小鼠之间的定量变化。Hedgehog酰基转移酶的转录不受LIF和E2注射的影响。总之，LIF，这有一个至关重要的作用，在E2的行动开始植入，引起短暂的诱导Pgr mRNA和随后的上调Ihh mRNA，介导孕酮Pgr行动成功植入。
Leukemia inhibitory factor (LIF) and Indian hedgehog (Ihh) are essential for embryo implantation in mice and are regulated by the actions of 17beta-estradiol (E2) and progesterone, respectively. The present study examined the effect of LIF on Ihh and Ihh-related factors in the uterine luminal epithelium during the implantation period using a DNA microarray. Expression of Ihh mRNA reached its peak on the forth day of pregnancy, and progesterone receptor (Pgr) mRNA decreased on the fifth day of pregnancy in wildtype mice. On the other hand, these changes in expression were not seen in LIF-/- mice. Ihh and Pgr mRNA were upregulated by LIF injection in delayed implantation mice. This up-regulation of Pgr was transient and preceded an increase of Ihh mRNA. Ihh mRNA also increased after E2 injection in delayed implantation mice of the LIF-/- genotype. E2 did not affect transcription of Pgr mRNA in the uterine luminal epithelium of delayed implantation LIF-/- mice. Using an antibody against the C-terminal epitope of Ihh, unprocessed Ihh proteins, but not C-terminal peptides, by autoproteolytic cleavage of Ihh were detected by western blot analysis. Unprocessed Ihh did not show quantitative changes between the wildtype and LIF-/- mice during the implantation period. Transcription of hedgehog acyltransferase was not influenced by LIF and E2 injection. In conclusion, LIF, which has a crucial role in E2 action for initiation of implantation, caused transient induction of Pgr mRNA and subsequent upregulation of Ihh mRNA, which mediates progesterone-Pgr actions for successful implantation.