Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair

摘要: Hepatocyte growth factor/scatter factor c-met signaling pathway is of central importance during development as well in tumorigenesis. Because homozygous null mice for either hgf/sf or die utero, we used Cre/loxP-mediated gene targeting to investigate the function specifically adult liver. Loss appeared not be detrimental hepatocyte under physiological conditions. Nonetheless, adaptive responses liver injury were dramatically affected. Mice lacking hepatocytes hypersensitive Fas-induced apoptosis. When injected with a low dose anti-Fas antibody, majority these died from massive apoptosis and hemorrhagic necrosis, whereas all wild-type survived signs minor injury. After challenge single necrogenic CCl4, conditional knockout exhibited impaired recovery centrolobular lesions rather than deficit proliferation. The delayed healing was associated persistent inflammatory reaction, over-production osteopontin, early prominent dystrophic calcification, scattering/migration into diseased areas. These studies provide direct genetic evidence support critical role efficient regeneration suggest that disruption affects primarily survival tissue remodeling.