{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:07:54Z","timestamp":1793041674457,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T00:00:00Z","timestamp":1450828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>\n                    Collagen stabilization through irreversible cross\u2010linking is thought to promote hepatic fibrosis progression and limit its reversibility. However, the mechanism of this process remains poorly defined. We studied the functional contribution of lysyl oxidase (LOX) to collagen stabilization and hepatic fibrosis progression\/reversal\n                    <jats:italic>in vivo<\/jats:italic>\n                    using chronic administration of irreversible LOX inhibitor \u03b2\u2010aminopropionitrile (BAPN, or vehicle as control) in C57Bl\/6J mice with carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )\u2010induced fibrosis. Fibrotic matrix stability was directly assessed using a stepwise collagen extraction assay and fibrotic septae morphometry. Liver cells and fibrosis were studied by histologic, biochemical methods and quantitative real\u2010time reverse\u2010transcription PCR. During fibrosis progression, BAPN administration suppressed accumulation of cross\u2010linked collagens, and fibrotic septae showed widening and collagen fibrils splitting, reminiscent of remodeling signs observed during fibrosis reversal. LOX inhibition attenuated hepatic stellate cell activation markers and promoted F4\/80\u2010positive scar\u2010associated macrophage infiltration without an increase in liver injury. In reversal experiments, BAPN\u2010treated fibrotic mice demonstrated accelerated fibrosis reversal after CCl4 withdrawal. Our findings demonstrate for the first time that LOX contributes significantly to collagen stabilization in liver fibrosis, promotes fibrogenic activation of attenuated hepatic stellate cells, and limits fibrosis reversal. Our data support the concept of pharmacologic targeting of LOX pathway to inhibit liver fibrosis and promote its resolution.\u2014Liu, S. B., Ikenaga, N., Peng, Z.\u2010W., Sverdlov, D. Y., Greenstein, A., Smith, V., Schuppan, D., Popov, Y. Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    30, 1599\u20131609 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-268425","type":"journal-article","created":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T23:35:56Z","timestamp":1450913756000},"page":"1599-1609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":211,"title":["Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice"],"prefix":"10.1096","volume":"30","author":[{"given":"Susan B.","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ikenaga","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen\u2010Wei","family":"Peng","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center, Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Oncology The First Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna Y.","family":"Sverdlov","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Greenstein","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. 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