{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:42:15Z","timestamp":1787067735959,"version":"build-2736575974"},"reference-count":47,"publisher":"American Physiological Society","issue":"5","funder":[{"name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","award":["RO1DK53804"],"award-info":[{"award-number":["RO1DK53804"]}]},{"name":"HHS | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAA)","award":["R21 AA021443"],"award-info":[{"award-number":["R21 AA021443"]}]},{"name":"NCI","award":["RO1CA092479"],"award-info":[{"award-number":["RO1CA092479"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:p>\n                    Epidermal growth factor receptor (EGFR) and its ligands have been implicated in liver fibrosis. However, it has not been directly shown that hepatocellular genetic ablation of either this receptor tyrosine kinase or ERBB3, its interactive signaling partner, affects hepatic fibrosis. Carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )-induced liver fibrosis in hepatocyte-specific (HS) mouse models of EGFR and ERBB3 ablation was evaluated in both single gene knockouts and an HS-EGFR-ERBB3 double knockout (DKO). Loss of hepatocellular EGFR or ERBB3 did not impact cytochrome P450-2E1 expression, the extent of centrilobular injury, or the initial regenerative response, but it did diminish liver fibrosis induced by chronic intraperitoneal administration of CCl\n                    <jats:sub>4<\/jats:sub>\n                    . The reduction of liver fibrosis correlated with reduced \u03b1-smooth muscle actin expression. Maximal impact to fibrogenesis occurred in the ERBB3 and EGFR-ERBB3 DKO models, suggesting that EGFR-ERBB3 heterodimeric signaling in damaged hepatocytes may play a more important role in liver fibrosis than EGFR-EGFR homodimeric signaling. Immunohistochemical analyses of phospho-EGFR and phospho-ERBB3 isoforms revealed clear staining in hepatocytes, activated stellate cells, and macrophages. Our results support a role for the hepatocellular ERBB tyrosine kinases in fibrogenesis and suggest that pharmacologic inhibition of EGFR-ERBB3 signaling may reverse or retard hepatic fibrosis.\n                  <\/jats:p>","DOI":"10.1152\/ajpgi.00423.2015","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T21:59:44Z","timestamp":1472767184000},"page":"G807-G816","source":"Crossref","is-referenced-by-count":33,"title":["Hepatocyte ERBB3 and EGFR are required for maximal CCl\n                    <sub>4<\/sub>\n                    -induced liver fibrosis"],"prefix":"10.1152","volume":"311","author":[{"given":"Lawrence A.","family":"Scheving","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University 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