{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:27:07Z","timestamp":1768480027835,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 DK\u2010067489"],"award-info":[{"award-number":["RO1 DK\u2010067489"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011620","name":"Liver Center, Saint Louis University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011620","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives:<\/jats:title><jats:p>Homozygous ZZ \u03b1\u20101\u2010antitrypsin (a1AT) deficiency is a common genetic liver disease that causes liver injury and hepatocellular carcinoma (HCC). The a1AT mutant Z gene encodes a mutant protein that accumulates within hepatocytes leading to hepatocellular death and a hepatic regenerative response. However, the mechanisms linking hepatocellular injury to these responses are poorly understood. In this study, we examined liver injury and response in human liver and in transgenic mice for involvement of hepatic progenitor cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Liver biopsy specimens of low\u2010grade, early\u2010stage human ZZ liver exhibiting minimal inflammation and minimal fibrosis (grade 1 and stage 1) were examined for hepatic progenitor cell (HPC) proliferation using immunoreactivity for cytokeratin\u20107 (CK\u20107). Transgenic mouse model liver and other selected human biopsies were also examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Increased CK\u20107\u2010positive HPC proliferation was seen in human ZZ liver compared to normal liver, but was 5\u2010fold less HPC proliferation than in grade\u2010 and stage\u2010matched disease control hepatitis C\u2013infected liver. Livers from PiZ mice, a model transgenic for the human a1AT mutant Z gene, which recapitulates the human injury, also showed HPC proliferation. Human ZZ liver and PiZ mice develop dysplasia in the liver and HCC. HCC in PiZ mice was also characterized by HPC proliferation. Progressive hepatic fibrosis with age in the PiZ mice is demonstrated for the first time in the present study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Chronic injury in both ZZ human and PiZ mouse liver is associated with hepatic fibrosis and a unique magnitude of HPC proliferation within the hepatic proliferative response.<\/jats:p><\/jats:sec>","DOI":"10.1097\/mpg.0b013e3181e7ff55","type":"journal-article","created":{"date-parts":[[2010,9,30]],"date-time":"2010-09-30T10:50:02Z","timestamp":1285843802000},"page":"626-630","source":"Crossref","is-referenced-by-count":23,"title":["Hepatic Progenitor Cell Proliferation and Liver Injury in \u03b1\u20101\u2010Antitrypsin Deficiency"],"prefix":"10.1002","volume":"51","author":[{"given":"Elizabeth M","family":"Brunt","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology of the Washington University School of Medicine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Blomenkamp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saint Louis University School of Medicine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muneeb","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saint Louis University School of Medicine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faiza","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saint Louis University School of Medicine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Marcus","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saint Louis University School of Medicine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Teckman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saint Louis University School of Medicine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-985072"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/357605a0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-006-0059-8"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.168.7.818"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20508"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20118"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21326"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00175.2003"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21822"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00041.2002"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00237.2004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508652200"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5722"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21009"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20815"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.279.5.G961"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2007.01470.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20130"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.05.012"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113580"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20650"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.1993.tb00029.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.1990.tb00453.x"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21832"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198603203141202"},{"key":"e_1_2_6_27_1","first-page":"307","volume-title":"Falk Symposium 115: Liver Cirrhosis and Its Development","author":"Eriksson S","year":"2001"}],"container-title":["Journal of Pediatric Gastroenterology and Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1097\/MPG.0b013e3181e7ff55","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T13:08:25Z","timestamp":1705583305000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1097\/MPG.0b013e3181e7ff55"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,11]]}},"alternative-id":["10.1097\/MPG.0b013e3181e7ff55"],"URL":"https:\/\/doi.org\/10.1097\/mpg.0b013e3181e7ff55","archive":["Portico"],"relation":{},"ISSN":["0277-2116","1536-4801"],"issn-type":[{"value":"0277-2116","type":"print"},{"value":"1536-4801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11]]}}}