{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:05:08Z","timestamp":1761919508924},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T00:00:00Z","timestamp":1330560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["552409"],"award-info":[{"award-number":["552409"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives:<\/jats:title><jats:p>Liver disease contributes to significant morbidity and mortality in cystic fibrosis (CF). Although all patients with CF express the defective CF transmembrane conductance regulator in cholangiocytes, many develop asymptomatic fibrosing liver disease. Only some develop cirrhosis, with pathogenesis remaining enigmatic. Available noninvasive diagnostic tools do not identify patients at risk before development of advanced fibrosis. We conducted a pilot study to identify genes associated with hepatic injury and fibrosis on liver biopsy that may help elucidate determinants of CF\u2010associated liver disease (CFLD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Liver tissue from children with CFLD with various stages of hepatic fibrosis was compared with pediatric controls using cDNA array analysis. Differential expression of genes of interest was then assessed relative to pediatric control liver and non\u2010CF cholestatic disease control liver from patients with biliary atresia, using both real\u2010time reverse transcription\u2010polymerase chain reaction and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>cDNA array demonstrated differential expression of numerous genes associated with hepatic fibrogenesis including collagens, matrix metalloproteinases, and chemokines in CFLD versus normal controls, particularly decreased expression in tissue remodeling genes including plasminogen activator inhibitor\u20101 (PAI\u20101, up to 25\u2010fold) and tissue inhibitor of metalloproteinase\u20101 (TIMP\u20101); this was validated by real\u2010time reverse transcription\u2010polymerase chain reaction (PAI\u20101, <jats:italic>P<\/jats:italic> = 0.004; TIMP\u20101, <jats:italic>P<\/jats:italic> = 0.019). No significant decrease in PAI\u20101 or TIMP\u20101 mRNA was observed in biliary atresia versus normal control. Immunohistochemistry confirmed the decreased expression of hepatic PAI\u20101 and TIMP\u20101 protein in CFLD versus both normal and biliary atresia disease controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>The coordinated differential expression of these genes associated with liver fibrosis provides evidence for a transcriptional basis for the pathogenesis of CFLD and provides avenues for further study. Clarifying the pathogenesis of CFLD will facilitate techniques for early, precirrhotic detection and targeted interventions.<\/jats:p><\/jats:sec>","DOI":"10.1097\/mpg.0b013e3182432034","type":"journal-article","created":{"date-parts":[[2011,12,8]],"date-time":"2011-12-08T11:17:51Z","timestamp":1323343071000},"page":"328-335","source":"Crossref","is-referenced-by-count":23,"title":["Transcriptional Basis for Hepatic Fibrosis in Cystic Fibrosis\u2013associated Liver Disease"],"prefix":"10.1002","volume":"54","author":[{"given":"Tamara N.","family":"Pereira","sequence":"first","affiliation":[{"name":"Hepatic Fibrosis Group The Queensland Institute of Medical Research The University of Queensland Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Lewindon","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group The Queensland Institute of Medical Research The University of Queensland Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ristan M.","family":"Greer","sequence":"additional","affiliation":[{"name":"School of Veterinary Science The University of Queensland Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita C.","family":"Hoskins","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group The Queensland Institute of Medical Research The University of Queensland Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard M.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Pathology The University of Queensland Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross W.","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group The Queensland Institute of Medical Research The University of Queensland Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant A.","family":"Ramm","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group The Queensland Institute of Medical Research The University of Queensland Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2570460"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2475911"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2772657"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300527"},{"key":"e_1_2_7_6_1","volume-title":"Cystic Fibrosis Foundation Annual Data Base 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