{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:04:45Z","timestamp":1792782285443,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T00:00:00Z","timestamp":1463011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Finnish Pediatric Research Foundation"},{"name":"Sigrid Juselius Foundation","id":[{"id":"https:\/\/ror.org\/00ckakm23","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Research Foundation of Helsinki University Hospital","id":[{"id":"https:\/\/ror.org\/02e8hzf44","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The molecular mechanisms underlying progressive liver fibrosis following surgical treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic gene and protein expression and serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after successful portoenterostomy (PE), and relate them to histological signs of liver injury, clinical follow\u2010up data and biochemical markers of hepatic function. LIver biopsies and serum samples were obtained from 25 children after successful PE at median age of 3.3 years. Serum MMP concentrations were determined by enzyme\u2010linked immune sorbent assay. Hepatic gene expression of MMPs and TIMPs was analyzed using real\u2010time reverse\u2010transcription PCR. Liver expression of MMP\u20107 and cytokeratin\u20107 was studied using immunohistochemistry. Despite effective clearance of biochemical and histological cholestasis following PE, BA patients showed increased hepatic gene expression of\n                    <jats:italic>MMP\u20107<\/jats:italic>\n                    (29\u2010fold,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001),\n                    <jats:italic>MMP\u20102<\/jats:italic>\n                    (3.1\u2010fold,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001),\n                    <jats:italic>MMP\u201014<\/jats:italic>\n                    (1.7\u2010fold,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007), and\n                    <jats:italic>TIMP\u20101<\/jats:italic>\n                    (1.8\u2010fold,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), when compared to controls. Similar to a biliary epithelial marker cytokeratin\u20107, expression of MMP\u20107 localized in biliary epithelium of bile ducts and ductal proliferations and periportal hepatocytes and was increased (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) in relation to controls. BA patients had 6\u2010fold higher serum levels of MMP\u20107 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), which correlated positively with hepatic\n                    <jats:italic>MMP\u20107<\/jats:italic>\n                    gene (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.548,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007) and protein (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.532,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007) expression. Patients showed a positive correlation between biliary MMP\u20107 expression and Metavir fibrosis stage (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.605,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001) and portal fibrosis grade (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.606,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001). Neither similarly increased MMP\u20107 expression nor correlation with liver fibrosis was observed in patients with intestinal failure\u2010associated liver disease and comparable Metavir stage. In conclusion, our findings support an unique role of altered hepatic expression of MMP\u20107 in the progression of liver fibrosis after successful PE and introduce a potential therapeutic target to pharmacologically extend native liver survival by inhibiting MMP\u20107 hyperactivity. Serum MMP\u20107 may be a valuable postoperative prognostic tool in BA.\n                  <\/jats:p>","DOI":"10.1002\/cjp2.50","type":"journal-article","created":{"date-parts":[[2016,4,30]],"date-time":"2016-04-30T05:19:30Z","timestamp":1461993570000},"page":"187-198","source":"Crossref","is-referenced-by-count":75,"title":["Increased MMP\u20107 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia"],"prefix":"10.1002","volume":"2","author":[{"given":"Anna","family":"Kerola","sequence":"first","affiliation":[{"name":"Pediatric Surgery and Pediatric Transplantation Surgery, Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki and Helsinki University Hospital Helsinki Finland"},{"name":"Department of Surgery North Karelia Central Hospital Joensuu 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