{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:26:29Z","timestamp":1791404789356,"version":"4.3.3"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,3,30]]},"abstract":"<jats:p>\n                    Hepatocyte growth factor\/scatter factor\n                    <jats:italic>c-met<\/jats:italic>\n                    signaling pathway is of central importance during development as well as in tumorigenesis. Because homozygous null mice for either\n                    <jats:italic>hgf<\/jats:italic>\n                    \/\n                    <jats:italic>sf<\/jats:italic>\n                    or\n                    <jats:italic>c-met<\/jats:italic>\n                    die\n                    <jats:italic>in utero<\/jats:italic>\n                    , we used Cre\/\n                    <jats:italic>lox<\/jats:italic>\n                    P-mediated gene targeting to investigate the function of\n                    <jats:italic>c-met<\/jats:italic>\n                    specifically in the adult liver. Loss of\n                    <jats:italic>c-met<\/jats:italic>\n                    appeared not to be detrimental to hepatocyte function under physiological conditions. Nonetheless, the adaptive responses of the liver to injury were dramatically affected. Mice lacking\n                    <jats:italic>c-met<\/jats:italic>\n                    gene in hepatocytes were hypersensitive to Fas-induced apoptosis. When injected with a low dose of anti-Fas antibody, the majority of these mice died from massive apoptosis and hemorrhagic necrosis, whereas all wild-type mice survived with signs of minor injury. After a challenge with a single necrogenic dose of CCl\n                    <jats:sub>4<\/jats:sub>\n                    ,\n                    <jats:italic>c-met<\/jats:italic>\n                    conditional knockout mice exhibited impaired recovery from centrolobular lesions rather than a deficit in hepatocyte proliferation. The delayed healing was associated with a persistent inflammatory reaction, over-production of osteopontin, early and prominent dystrophic calcification, and impaired hepatocyte scattering\/migration into diseased areas. These studies provide direct genetic evidence in support of the critical role of\n                    <jats:italic>c-met<\/jats:italic>\n                    in efficient liver regeneration and suggest that disruption of\n                    <jats:italic>c-met<\/jats:italic>\n                    affects primarily hepatocyte survival and tissue remodeling.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0306068101","type":"journal-article","created":{"date-parts":[[2004,3,30]],"date-time":"2004-03-30T14:58:04Z","timestamp":1080658684000},"page":"4477-4482","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":681,"title":["Hepatocyte growth factor\/\n                    <i>c-met<\/i>\n                    signaling pathway is required for efficient liver regeneration and repair"],"prefix":"10.1073","volume":"101","author":[{"given":"Chang-Goo","family":"Huh","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4262, Building 37, Room 4146A, Bethesda, MD 20892-4262"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina M.","family":"Factor","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4262, Building 37, Room 4146A, Bethesda, MD 20892-4262"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ar\u00e1nzazu","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4262, Building 37, Room 4146A, Bethesda, MD 20892-4262"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Uchida","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4262, Building 37, Room 4146A, Bethesda, MD 20892-4262"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Conner","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4262, Building 37, Room 4146A, Bethesda, MD 20892-4262"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snorri S.","family":"Thorgeirsson","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4262, Building 37, Room 4146A, Bethesda, MD 20892-4262"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,3,30]]},"reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.60"},{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a021283"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10358"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(98)01359-2"},{"key":"e_1_3_1_5_2","first-page":"119","volume":"212","year":"1997","unstructured":"Vande Woude, G. 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