Journal article
Placenta-specific protein 1 (PLAC1) expression is significantly down-regulated in preeclampsia via a hypoxia-mediated mechanism
The journal of maternal-fetal & neonatal medicine, Vol.35(25), pp.8419-8425
12/12/2022
DOI: 10.1080/14767058.2021.1977792
PMCID: PMC8959068
PMID: 34565269
Abstract
Examine a mechanism of PLAC1 regulation and its potential role in preeclampsia (PE).
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).
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 (r
2
= 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.
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.
Details
- Title: Subtitle
- Placenta-specific protein 1 (PLAC1) expression is significantly down-regulated in preeclampsia via a hypoxia-mediated mechanism
- Creators
- Eric J. Devor - Roy J. and Lucille A. Carver College of MedicineDonna A. Santillan - University of IowaAkshaya Warrier - Roy J. and Lucille A. Carver College of MedicineSabrina M. Scroggins - University of IowaMark K. Santillan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The journal of maternal-fetal & neonatal medicine, Vol.35(25), pp.8419-8425
- DOI
- 10.1080/14767058.2021.1977792
- PMID
- 34565269
- PMCID
- PMC8959068
- NLM abbreviation
- J Matern Fetal Neonatal Med
- ISSN
- 1476-7058
- eISSN
- 1476-4954
- Publisher
- Taylor & Francis
- Grant note
- name: National Institutes of Health (NIH) Clinical and Translational Science Award, award: U54TR001356; name: National Institutes of Health Reproductive Scientist Development Program, award: K12HD00849; DOI: 10.13039/100000968, name: American Heart Association, award: 15SFRN23480000, 15SFRN23730000, 15SFRN23760002, 15SFRN23860007; name: University of Iowa Interdisciplinary Immunology Postdoctoral Training Program; name: University of Iowa Department of Obstetrics and Gynecology; name: University of Iowa Center for Hypertension Research; name: Shelly Bridgewater Dreams Foundation; name: Swift Family Foundation; name: NIH/NCI, award: P30CA086862
- Language
- English
- Date published
- 12/12/2022
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984318221602771
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