Journal
CELLS
Volume 11, Issue 14, Pages -Publisher
MDPI
DOI: 10.3390/cells11142259
Keywords
developing human blood-brain barrier (BBB); P-glycoprotein (P-gp; ABCB1); breast cancer resistance protein (BCRP; ABCG2); fetal brain endothelial cells (BECs); tube formation
Categories
Funding
- Canadian Institutes for Health Research (CIHR) [FDN-148368]
- Coordenacao de Aperfeicoamento Pessoal de Nivel Superior (CAPES) [001, 88887.370196/2019-00]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [10578/2020-5]
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) [APQ-00338-18]
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There is limited information about the expression and function of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in the developing blood-brain barrier (BBB). In this study, primary human fetal brain endothelial cells (hfBECs) from early and mid-gestation brains were isolated and cultured to assess the expression and function of P-gp and BCRP. The results showed that both P-gp and BCRP are expressed and functionally competent in hfBECs from early and mid-gestation, indicating their potential role in the protective phenotype of the BBB during early stages of pregnancy.
There is little information about the functional expression of the multidrug resistance (MDR) transporters P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2) in the developing blood-brain barrier (BBB). We isolated and cultured primary human fetal brain endothelial cells (hfBECs) from early and mid-gestation brains and assessed P-gp/ABCB1 and BCRP/ABCG2 expression and function, as well as tube formation capability. Immunolocalization of the von Willebrand factor (marker of endothelial cells), zonula occludens-1 and claudin-5 (tight junctions) was detected in early and mid-gestation-derived hfBECs, which also formed capillary-like tube structures, confirming their BEC phenotype. P-gp and BCRP immunostaining was detected in capillary-like tubes and in the cytoplasm and nucleus of hfBECs. P-gp protein levels in the plasma membrane and nuclear protein fractions, as well as P-gp protein/ABCB1 mRNA and BCRP protein levels decreased (p < 0.05) in hfBECs, from early to mid-gestation. No differences in P-gp or BCRP activity in hfBECs were observed between the two age groups. The hfBECs from early and mid-gestation express functionally competent P-gp and BCRP drug transporters and may thus contribute to the BBB protective phenotype in the conceptus from early stages of pregnancy.
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