Low oxygen tension differentially regulates the expression of placental solute carriers and ABC transporters.
Ludwik GorczycaJianyao DuKristin M BircsakXia WenAnna M VetranoLauren M AleksunesPublished in: FEBS letters (2020)
Low oxygen concentration, or hypoxia, is an important physiological regulator of placental function including chemical disposition. Here, we compared the ability of low oxygen tension to alter the expression of solute carriers (SLC) and ABC transporters in two human placental models, namely BeWo cells and term placental explants. We found that exposure to low oxygen concentration differentially regulates transporter expression in BeWo cells, including downregulation of ENT1, OATP4A1, OCTN2, BCRP, and MRP2/3/5, and upregulation of CNT1, OAT4, OATP2B1, SERT, SOAT, and MRP1. Similar upregulation of MRP1 and downregulation of MRP5 and BCRP were observed in explants, whereas uptake transporters were decreased or unchanged. Furthermore, a screening of transcriptional regulators of transporters revealed that hypoxia leads to a decrease in the mRNA levels of aryl hydrocarbon receptor, nuclear factor erythroid 2-related factor 2, and retinoid x receptor alpha in both human placental models. These data suggest that transporter expression is differentially regulated by oxygen concentration across experimental human placental models.
Keyphrases
- poor prognosis
- endothelial cells
- binding protein
- induced apoptosis
- nuclear factor
- signaling pathway
- cell proliferation
- long non coding rna
- transcription factor
- toll like receptor
- pluripotent stem cells
- gene expression
- preterm infants
- cell cycle arrest
- machine learning
- oxidative stress
- single cell
- artificial intelligence
- big data
- immune response
- deep learning