{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:42Z","timestamp":1772168982698,"version":"3.50.1"},"reference-count":36,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["ECR\/2015\/000275"],"award-info":[{"award-number":["ECR\/2015\/000275"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR15116\/MED\/31\/334\/2016"],"award-info":[{"award-number":["BT\/PR15116\/MED\/31\/334\/2016"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    Bile salt export pump (BSEP\/ABCB11) is important in the maintenance of the enterohepatic circulation of bile acids and drugs. Drugs such as rifampicin and glibenclamide inhibit BSEP. Progressive familial intrahepatic cholestasis type-2, a lethal pediatric disease, some forms of intrahepatic cholestasis of pregnancy, and drug-induced cholestasis are associated with BSEP dysfunction.\u00a0\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    We started with a bioinformatic approach to identify the relationship between ABCB11 and other proteins, microRNAs, and drugs. A microarray data set of the liver samples from ABCB11 knockout mice was analyzed using GEO2R. Differentially expressed gene pathway enrichment analysis was conducted using ClueGo. A protein-protein interaction network was constructed using STRING application in Cytoscape. Networks were analyzed using Cytoscape. CyTargetLinker was used to screen the transcription factors, microRNAs and drugs. Predicted drugs were validated on human liver cell line, HepG2. BSEP expression was quantified by real-time PCR and western blotting.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results:<\/ns3:bold>\n                    <ns3:italic>ABCB11<\/ns3:italic>\n                    knockout in mice was associated with a predominant upregulation and downregulation of genes associated with cellular component movement and sterol metabolism, respectively. We further identified the hub genes in the network. Genes related to immune activity, cell signaling, and fatty acid metabolism were dysregulated.\u00a0 We further identified drugs (glibenclamide and ATP) and a total of 14 microRNAs targeting the gene. Western blot and real-time PCR analysis confirmed the upregulation of BSEP on the treatment of HepG2 cells with glibenclamide, ATP, and metformin.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions:<\/ns3:bold>\n                    The differential expression of cell signaling genes and those related to immune activity in\n                    <ns3:italic>ABCB11<\/ns3:italic>\n                    KO animals may be secondary to cell injury. We have found glibenclamide, ATP, and metformin upregulates BSEP. The mechanisms involved and the clinical relevance of these findings need to be investigated.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.26632.1","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T11:10:20Z","timestamp":1608635420000},"page":"1497","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Glibenclamide, ATP and metformin increases the expression of human bile salt export pump ABCB11"],"prefix":"10.12688","volume":"9","author":[{"given":"Nisha","family":"Vats","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi Chandra","family":"Dubey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0007-5718","authenticated-orcid":false,"given":"Madhusudana Girija","family":"Sanal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pankaj","family":"Taneja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senthil Kumar","family":"Venugopal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1203-1214","DOI":"10.1053\/j.gastro.2008.01.038","article-title":"Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.","volume":"134","author":"S Strautnieks","year":"2008","journal-title":"Gastroenterology."},{"key":"ref-2","first-page":"2029-2034","article-title":"Identification of a sister gene to P-glycoprotein.","volume":"55","author":"S Childs","year":"1995","journal-title":"Cancer 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.29399.r76410, Premkumar Kumpati, Department of Biomedical Science, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India, 25 Jan 2021, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-1497\/v1#referee-response-76410","order":0,"name":"referee-response-76410","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.29399.r76680, Jayanta Roy-Chowdhury, Department of Medicine, Montefiore Medical Center, Bronx, NY, USA, 03 Feb 2021, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-1497\/v1#referee-response-76680","order":1,"name":"referee-response-76680","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.29399.r79055, Amit Dash, Baylor College of Medicine, Houston, TX, USA, 09 Mar 2021, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-1497\/v1#referee-response-79055","order":2,"name":"referee-response-79055","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The corresponding author (Sanal MG) acknowledges the Science and Engineering Research Board (SERB), Government of India (ECR\/2015\/000275) and the Department of Biotechnology (DBT), Government of India (BT\/PR15116\/MED\/31\/334\/2016) for a limited financial support for approximately 18 months. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}