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Low oxygen tension differentially regulates the expression of placental solute carriers and ABC transporters
Author(s) -
Gorczyca Ludwik,
Du Jianyao,
Bircsak Kristin M.,
Wen Xia,
Vetrano Anna M.,
Aleksunes Lauren M.
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13937
Subject(s) - downregulation and upregulation , multidrug resistance associated protein 2 , oxygen tension , transporter , hypoxia (environmental) , solute carrier family , microbiology and biotechnology , aryl hydrocarbon receptor , abcg2 , biology , chemistry , receptor , atp binding cassette transporter , biochemistry , oxygen , transcription factor , gene , organic chemistry
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.