title: PLAC4 is upregulated in severe early onset preeclampsia and upregulated with syncytialisation but not hypoxia.
abstract: BACKGROUND
  Severe early onset preeclampsia is one of the most serious complications of pregnancy. Placental specific 4 (PLAC4) is very highly expressed in placenta relative to all other tissues. Recently in a biomarker screening study, we found PLAC4 mRNA was significantly upregulated in maternal whole blood and placenta obtained from cases of severe preeclampsia. Intriguingly however, very little is known about its expression or functional role in either normal pregnancy or pregnancies complicated by preeclampsia.
  
  
  METHODS
  The objective of this study was to characterize the protein expression and localization of PLAC4 in severe early onset preeclamptic placenta. Given so little of the biology of PLAC4 is known, we also examined whether the expression of PLAC4 alters with syncytialisation or placental hypoxia.
  
  
  RESULTS
  We found PLAC4 protein expression was significantly (p < 0.05) upregulated in severe early onset preeclamptic placentas (n = 24) compared to gestationally matched preterm controls (n = 12). PLAC4 protein was specifically localized to the syncytiotrophoblast of preterm, preeclamptic and term placentas. Functional analysis of PLAC4 mRNA and protein expression revealed a significant (p < 0.05) increase with syncytialisation of BeWo cells. However, exposure of either syncytialised BeWo cells or primary term placental explants to hypoxia (1% oxygen) did not alter the expression of either PLAC4 mRNA or protein.
  
  
  CONCLUSIONS
  In conclusion, we have found PLAC4 is significantly upregulated in association with severe preterm preeclampsia. Furthermore, it is upregulated with syncytialisation, but not hypoxia. It is possible PLAC4 may have a role in the pathogenesis of preeclampsia, and its biology merits further investigation.
authors: The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors: L
authors: L
authors: Tuohey
authors: K
authors: K
authors: Macintire
authors: L
authors: L
authors: Ye
authors: K
authors: K
authors: Palmer
authors: M
authors: M
authors: Skubisz
authors: S
authors: S
authors: Tong
authors: T J
authors: TJ
authors: Kaitu'u-Lino
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D002459:Cell Fusion; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D001798:Blood Proteins; C583016:PLAC4 protein, human; D011257:Pregnancy Proteins; D005576:Colforsin