| First Author | Huh CG | Year | 2004 |
| Journal | Proc Natl Acad Sci U S A | Volume | 101 |
| Issue | 13 | Pages | 4477-82 |
| PubMed ID | 15070743 | Mgi Jnum | J:89236 |
| Mgi Id | MGI:3039209 | Doi | 10.1073/pnas.0306068101 |
| Citation | Huh CG, et al. (2004) Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci U S A 101(13):4477-82 |
| abstractText | Hepatocyte growth factor/scatter factor c-met signaling pathway is of central importance during development as well as in tumorigenesis. Because homozygous null mice for either hgf/sf or c-met die in utero, we used Cre/loxP-mediated gene targeting to investigate the function of c-met specifically in the adult liver. Loss of c-met 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 c-met 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 CCl4, c-met 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 c-met in efficient liver regeneration and suggest that disruption of c-met affects primarily hepatocyte survival and tissue remodeling. |
