The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2021
Placenta-specific protein 1 (PLAC1) expression is significantly down-regulated in preeclampsia via a hypoxia-mediated mechanism.
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Devor Eric J, Santillan Donna A, Warrier Akshaya, Scroggins Sabrina M, Santillan Mark K
Аннотация
OBJECTIVE: Examine a mechanism of PLAC1 regulation and its potential role in preeclampsia (PE).
MATERIALS AND METHODS: Placental tissue samples and detailed clinical information were obtained through the University of Iowa Maternal Fetal Tissue Bank (IRB# 200910784) from gestational and maternal age-matched control (n = 17) and PE affected pregnancies (n = 12). PLAC1 and PLAC1 promoter-specific expression was measured using quantitative polymerase chain reaction (qPCR) and differences were assessed via the standard ΔΔCt method. In addition, the role of hypoxia in PLAC1 transcription was investigated through the exposure of HTR8/SVneo human trophoblast cells to the hypoxia mimic dimethyloxaloylglycine (DMOG).
RESULTS: PLAC1 expression is seen to be 8.9-fold lower in human placentas affected by preeclampsia in comparison with controls (p < .05). Further, this decrease is paralleled by a significantly lower expression of the P2 or proximal PLAC1 promoter (p < .05). Expression of mediator complex subunit 1 (MED1), a known hypoxia-sensitive transcription coactivator and PLAC1 effector, is significantly correlated with PLAC 1 expression (r2 = 0.607, p < .001). These data suggest that PLAC1 expression is significantly down-regulated in preeclampsia at least in part via a MED1 hypoxia-mediated mechanism.
CONCLUSIONS: We confirm that PLAC1 transcription is suppressed in the placentae of women affected by preeclampsia. We further demonstrate that this suppression is driven through the P2 or proximal PLAC1 promoter. This demonstration led to the identification of the MED1-TRAP cofactor complex as the hypoxia-sensitive driver.
MATERIALS AND METHODS: Placental tissue samples and detailed clinical information were obtained through the University of Iowa Maternal Fetal Tissue Bank (IRB# 200910784) from gestational and maternal age-matched control (n = 17) and PE affected pregnancies (n = 12). PLAC1 and PLAC1 promoter-specific expression was measured using quantitative polymerase chain reaction (qPCR) and differences were assessed via the standard ΔΔCt method. In addition, the role of hypoxia in PLAC1 transcription was investigated through the exposure of HTR8/SVneo human trophoblast cells to the hypoxia mimic dimethyloxaloylglycine (DMOG).
RESULTS: PLAC1 expression is seen to be 8.9-fold lower in human placentas affected by preeclampsia in comparison with controls (p < .05). Further, this decrease is paralleled by a significantly lower expression of the P2 or proximal PLAC1 promoter (p < .05). Expression of mediator complex subunit 1 (MED1), a known hypoxia-sensitive transcription coactivator and PLAC1 effector, is significantly correlated with PLAC 1 expression (r2 = 0.607, p < .001). These data suggest that PLAC1 expression is significantly down-regulated in preeclampsia at least in part via a MED1 hypoxia-mediated mechanism.
CONCLUSIONS: We confirm that PLAC1 transcription is suppressed in the placentae of women affected by preeclampsia. We further demonstrate that this suppression is driven through the P2 or proximal PLAC1 promoter. This demonstration led to the identification of the MED1-TRAP cofactor complex as the hypoxia-sensitive driver.