Increased immortalization-upregulated protein 2 (IMUP-2) by hypoxia induces apoptosis of the trophoblast and pre-eclampsia.

In regulation of the developmental process, the balance between cellular proliferation and cell death is critical. Placental development tightly controls this mechanism, and increased apoptosis of placental trophoblasts can cause a variety of gynecological diseases. Members of the immortalization-upregulated protein (IMUP) family are nuclear proteins implicated in SV40-mediated immortalization and cellular proliferation; however, the mechanisms by which their expression is regulated in placental development are still unknown. We compared IMUP-2 expression in normal and pre-eclamptic placental tissues and evaluated the function of IMUP-2 in HTR-8/SVneo trophoblast cells under hypoxic conditions. IMUP-2 was expressed in syncytiotrophoblasts and syncytial knots of the placental villi. IMUP-2 expression was significantly higher in preterm pre-eclampsia patients than in patients who went to term (P < 0.001); however, we observed no differences in IMUP-2 expression between normal term patients with and without pre-eclampsia. Hypoxic conditions increased apoptosis of HTR8/SVneo trophoblast cells and induced IMUP-2 expression. Also, apoptosis of HTR-8/SVneo trophoblast cells was increased after IMUP-2 gene transfection. These results suggest that IMUP-2 expression is specifically elevated in preterm pre-eclampsia and under hypoxic conditions, and that IMUP-2 induces apoptosis of the trophoblast. Therefore, IMUP-2 might have functional involvement in placental development and gynecological diseases such as pre-eclampsia.

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