RGD Reference Report - Human placental expression of SLIT/ROBO signaling cues: effects of preeclampsia and hypoxia. - Rat Genome Database

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Human placental expression of SLIT/ROBO signaling cues: effects of preeclampsia and hypoxia.

Authors: Liao, Wu-Xiang  Laurent, Louise C  Agent, Sally  Hodges, Jennifer  Chen, Dong-Bao 
Citation: Liao WX, etal., Biol Reprod. 2012 Apr 12;86(4):111. doi: 10.1095/biolreprod.110.088138. Print 2012 Apr.
RGD ID: 243048428
Pubmed: PMID:22262697   (View Abstract at PubMed)
PMCID: PMC3338657   (View Article at PubMed Central)
DOI: DOI:10.1095/biolreprod.110.088138   (Journal Full-text)

Preeclampsia is characterized by dysfunctional endothelium and impaired angiogenesis. Recent studies suggest that the neuronal guidance SLIT/ROBO system regulates tumor angiogenesis. This study investigated if SLIT and ROBO are differentially expressed in healthy term and preeclamptic placentas and if hypoxia regulates SLIT and ROBO expression in placental trophoblast and endothelial cells. Total RNA and protein were extracted from placental tissues of healthy term (n = 5) and preeclamptic (n = 6) pregnancies and used for SLIT/ROBO expression analyses with reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative-PCR, and immunoblotting. Paraffin-embedded tissues were processed to localize SLIT/ROBO proteins in placental villi by immunohistochemistry. BeWo choriocarcinoma cells and human umbilical vein endothelial cells (HUVEC) were treated with 2% or 10% oxygen or the hypoxia mimetic deferoxamine mesylate (100 μM) to test if hypoxia regulates SLIT/ROBO expression. SLIT2, SLIT3, ROBO1, and ROBO4 mRNA and proteins were detected in the placenta. SLIT2 and ROBO1 proteins localized in the syncytiotrophoblast, and SLIT3, ROBO1, and ROBO4 in capillary endothelium of the placental villi. Levels of ROBO1 and ROBO4 as well as sFLT1 (soluble fms-like tyrosine kinase-1) proteins were significantly greater in preeclamptic placentas compared to normal controls. Hypoxia significantly increased both mRNA and protein levels of SLIT2 in BeWo cells and of SLIT3, ROBO1, and ROBB4 in HUVEC. Thus, trophoblast and endothelial coexpression of SLIT/ROBO suggests an autocrine/paracrine regulatory system for regulating placental function. Differential expression of SLITs and ROBOs in healthy term and preeclamptic placentas and hypoxia regulation of their expressions in placental cells implicate a potential pathophysiological role for this system in preeclampsia.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FLT1Humanpre-eclampsia  IEP mRNA and protein:increased expression:placentaRGD 
Flt1Ratpre-eclampsia  ISOFLT1 (Homo sapiens)mRNA and protein:increased expression:placentaRGD 
Flt1Mousepre-eclampsia  ISOFLT1 (Homo sapiens)mRNA and protein:increased expression:placentaRGD 
ROBO1Humanpre-eclampsia  IEP mRNA and protein:increased expression:placentaRGD 
ROBO4Humanpre-eclampsia  IEP mRNA and protein:increased expression:placentaRGD 
Robo1Ratpre-eclampsia  ISOROBO1 (Homo sapiens)mRNA and protein:increased expression:placentaRGD 
Robo1Mousepre-eclampsia  ISOROBO1 (Homo sapiens)mRNA and protein:increased expression:placentaRGD 
Robo4Mousepre-eclampsia  ISOROBO4 (Homo sapiens)mRNA and protein:increased expression:placentaRGD 
Robo4Ratpre-eclampsia  ISOROBO4 (Homo sapiens)mRNA and protein:increased expression:placentaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Flt1  (Fms related receptor tyrosine kinase 1)
Robo1  (roundabout guidance receptor 1)
Robo4  (roundabout guidance receptor 4)

Genes (Mus musculus)
Flt1  (FMS-like tyrosine kinase 1)
Robo1  (roundabout guidance receptor 1)
Robo4  (roundabout guidance receptor 4)

Genes (Homo sapiens)
FLT1  (fms related receptor tyrosine kinase 1)
ROBO1  (roundabout guidance receptor 1)
ROBO4  (roundabout guidance receptor 4)


Additional Information