{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:05:05Z","timestamp":1790521505203,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19be0304101h0003"],"award-info":[{"award-number":["19be0304101h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    An understanding of the quantitative relationship between bile canaliculus (BC) dynamics and the disruption of tight junctions (TJs) during drug\u2010induced intrahepatic cholestasis may lead to new strategies aimed at drug development and toxicity testing. To investigate the relationship between BC dynamics and TJ disruption, we retrospectively analyzed the extent of TJ disruption in response to changes in the dynamics of BCs cultured with entacapone (ENT). Three hours after adding ENT, the ZO\u20101\u2010negative BC surface area ratio became significantly higher (4.1\u2010fold) than those of ZO\u20101\u2010positive BCs. Based on these data, we calculated slopes of surface area changes,\n                    <jats:italic>m<\/jats:italic>\n                    , of each ZO\u20101\u2010positive and ZO\u20101\u2010negative BC. BCs with\n                    <jats:italic>m<\/jats:italic>\n                    \u00a0\u2264\u00a015 that fell within the 95% confidence interval of ZO\u20101\u2010positive BCs were defined as ZO\u20101\u2010positive. To validate this method, we compared the frequency of ZO\u20101\u2010positive BCs,\n                    <jats:italic>F<\/jats:italic>\n                    <jats:sub>Z<\/jats:sub>\n                    , with that of BCs with\n                    <jats:italic>m<\/jats:italic>\n                    \u00a0\u2264\u00a015,\n                    <jats:italic>F<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    , in culture using drugs that regulate TJ, or induce intrahepatic cholestasis.\n                    <jats:italic>F<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    values were correlated with\n                    <jats:italic>F<\/jats:italic>\n                    <jats:sub>Z<\/jats:sub>\n                    under all culture conditions (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u00a0=\u00a0.99). Our results indicate that the magnitude of BC surface area changes is a factor affecting TJ disruption, suggesting that maintaining TJ integrity by slowing BC dilation inhibits cell death.\n                  <\/jats:p>","DOI":"10.1002\/prp2.960","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:16:45Z","timestamp":1653635805000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Quantitative understanding of HepaRG cells during drug\u2010induced intrahepatic cholestasis through changes in bile canaliculi dynamics"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-8942","authenticated-orcid":false,"given":"Rie","family":"Sonoi","sequence":"first","affiliation":[{"name":"Biomedical Research Institute National Institute of Advanced Industrial Science and Technology  Ikeda Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Hagihara","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute National Institute of Advanced Industrial Science and Technology  Ikeda Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/476217"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/157016312799304570"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2012.68515"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/c7lc00952f"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26822"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578\u2010021\u201000279\u2010y"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kft197"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5b00659"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.137.6.1421"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.116.071373"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24709"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.1.181"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.45.29745"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.058606"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10342"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010381326\u20108.00007\u20107"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018376108"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2008.06.014"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.60.1.121"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551\u2010019\u201000582\u20107"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2017.05.013"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfy101"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010006\u20100365\u20103"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2020.08.004"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009070698"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18\u201026260"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.9.2024"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200210020"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.006"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1342.029"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2005.07.007"},{"key":"e_1_2_12_34_1","first-page":"1","article-title":"Environmental considerations for live cell imaging","volume":"9","author":"Peters J","year":"2008","journal-title":"Nikon Application Notes"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c04377"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2014.05.025"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2018.07.020"}],"container-title":["Pharmacology Research &amp; 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