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.
Jeon
Su Yeon
SY
Department of Biomedical Science, CHA University, Seoul, Republic of Korea.
Lee
Hyun-Jung
HJ
Park
Ji Myeong
JM
Jung
Hyun Min
HM
Yoo
Jung Ki
JK
Lee
Hey-Jin
HJ
Lee
Jong-Sung
JS
Cha
Dong-Hyun
DH
Kim
Jin Kyeoung
JK
Kim
Gi Jin
GJ
D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D017931:DNA Primers; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D009687:Nuclear Proteins / Q000502:physiology*; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
C439765:C19orf33 protein, human; D017931:DNA Primers; D009687:Nuclear Proteins; D014157:Transcription Factors