{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:51:31Z","timestamp":1791467491051,"version":"4.3.4"},"reference-count":88,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN\u2010148368"],"award-info":[{"award-number":["FDN\u2010148368"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010191689"],"award-info":[{"award-number":["PJT\u2010191689"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["310489\/2023\u20107"],"award-info":[{"award-number":["310489\/2023\u20107"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["401189\/2025\u20102"],"award-info":[{"award-number":["401189\/2025\u20102"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ\u201000099\u201024"],"award-info":[{"award-number":["APQ\u201000099\u201024"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n P\u2010glycoprotein (P\u2010gp, encoded by\n ABCB1<\/jats:italic>\n ) and breast cancer resistance protein (BCRP\/\n ABCG2<\/jats:italic>\n ), present in the blood\u2013brain barrier, protect the fetal brain from exposure to neurotoxicants. P\u2010gp and BCRP are modulated by microRNA\u2010145\u20105p (miR\u2010145\u20105p) in cancer cells. In the present study, we hypothesized that miR\u2010145\u20105p modulates P\u2010gp and BCRP in human fetal brain endothelial cells (hfBECs) and in an adult BEC line (human cerebral microvascular endothelial cell line; hCMEC\/D3). miR\u2010145\u20105p mimic and inhibitor were transfected into hfBECs (\n n<\/jats:italic>\n \u00a0=\u00a06, mid\u2010gestation) and hCMEC\/D3 cells. P\u2010gp and BCRP mRNA, protein expression and efflux activity were assessed using qPCR, Western blotting, immunofluorescence and calcein\u2010AM and chlorin e6 assays. Target specificity was evaluated using luciferase reporter assays. hfBECs exhibited lower\n ABCB1<\/jats:italic>\n and\n ABCG2\u00a0<\/jats:italic>\n mRNA and protein expression and reduced P\u2010gp activity, but significantly increased BCRP activity, compared with hCMEC\/D3 cells. The miR\u2010145\u20105p mimic reduced luciferase activity of an\n ABCB1<\/jats:italic>\n 3\u2032\u2010untranslated region (3\u2019\u2010UTR) reporter but had no effect on the\n ABCG2<\/jats:italic>\n 3\u2032\u2010UTR. In hfBECs, miR\u2010145\u20105p overexpression reduced P\u2010gp and BCRP levels and efflux activity. In contrast, miR\u2010145\u20105p overexpression in hCMEC\/D3 cells increased P\u2010gp activity while reducing BCRP activity. Inhibition of miR\u2010145\u20105p in hfBECs increased P\u2010gp protein levels and exhibited a trend towards increased P\u2010gp activity, without altering BCRP levels, although BCRP activity significantly increased. miR\u2010145\u20105p directly modulates the expression and activity of P\u2010gp and indirectly modulates BCRP in fetal and adult human BECs. These data suggest that miR\u2010145\u20105p plays an important role in the regulation of key drug transporters at the BBB in fetal brain and may modulate BBB function in adulthood.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n microRNA\u2010145\u20105p (miR\u2010145\u20105p) directly targets the 3\u2032\u2010untranslated region (3\u2032\u2010UTR) of\n ABCB1<\/jats:italic>\n , but not\n ABCG2<\/jats:italic>\n , as shown by luciferase assays.\n <\/jats:p>\n <\/jats:list-item>\n \n In human fetal brain endothelial cells (hfBECs), miR\u2010145\u20105p mimic reduces P\u2010glycoprotein (P\u2010gp) and breast cancer resistance protein (BCRP) levels and transporter activity.<\/jats:p>\n <\/jats:list-item>\n \n Inhibition of miR\u2010145\u20105p in hfBECs increases P\u2010gp and BCRP activities.<\/jats:p>\n <\/jats:list-item>\n \n In adult human cerebral microvascular endothelial cell line (hCMEC\/D3) cells, miR\u2010145\u20105p mimic increases P\u2010gp activity and decreases BCRP activity, indicating developmental differences in regulation.<\/jats:p>\n <\/jats:list-item>\n \n miR\u2010145\u20105p directly modulates P\u2010gp and indirectly modulates BCRP, suggesting a key role in blood\u2013brain barrier (BBB) transporter regulation during fetal development and potentially in adulthood.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290712","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:56:27Z","timestamp":1791464187000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["microRNA\u2010145\u20105p regulates P\u2010glycoprotein and breast cancer resistance protein in primary human fetal brain endothelial cells"],"prefix":"10.1113","author":[{"given":"Phetcharawan","family":"Lye","sequence":"first","affiliation":[{"name":"Department of Physiology University of Toronto Toronto Ontario Canada"},{"name":"Lunenfeld\u2010Tanenbaum Research Institute Mount Sinai Hospital Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0275-8686","authenticated-orcid":false,"given":"Enrrico","family":"Bloise","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Toronto Toronto Ontario Canada"},{"name":"Department of Morphology Federal University of Minas Gerais Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5478-0872","authenticated-orcid":false,"given":"Nikola","family":"Ivanovski","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Toronto Toronto Ontario Canada"},{"name":"Lunenfeld\u2010Tanenbaum Research Institute Mount Sinai Hospital Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubna","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Lunenfeld\u2010Tanenbaum Research Institute Mount Sinai Hospital Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Casciaro","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Toronto Toronto Ontario Canada"},{"name":"Lunenfeld\u2010Tanenbaum Research Institute Mount Sinai Hospital Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9654-9940","authenticated-orcid":false,"given":"Stephen G.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Toronto Toronto Ontario Canada"},{"name":"Lunenfeld\u2010Tanenbaum Research Institute Mount Sinai Hospital Toronto Ontario Canada"},{"name":"Department of Obstetrics and Gynaecology University of Toronto Toronto Ontario Canada"},{"name":"Department of Medicine, Faculty of Medicine University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"1","key":"e_1_2_5_2_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood\u2010brain barrier","volume":"37","author":"Abbott N. 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