MMP-9 Deficiency Impairs Liver Regeneration Through EGFR Signaling In Partial Hepatectomy Mice

Background:Liver is the only organ which has powerful repair and regeneration ability. The more we understand about the mechanism involved, the more beneficial for treatment of liver disease. Current viewpoints indicate that liver regeneration is a complicated process regulated by many complex mechanisms, relating to cytokines, growth factors, metabolic networks, etc. Previous researches have demonstrated that matrix metalloproteinase-9 (MMP-9) is a vital factor in liver regeneration. The present study aims to explore the role of MMP-9 in epidermal growth factor receptor (EGFR) signaling and its downstream pathway in liver regeneration.Materials and Methods:All mice were used to establish the 70% partial hepatectomy (PH) model and randomized into three groups:Sham group, wild-type (WT) group, MMP-9 knockout (KO) group. After PH, Liver regeneration, EGFR ligands, EGFR and downstream factors were measured by liver weight to body weight ratio, qRT-PCR, ELISA, and western blot, etc.Results:After PH, MMP-9 KO mice showed a delayed liver regenerative response. EGFR ligands(HB-EGF and amphiregulin) were expressed at significantly lower levels between days 1 and 3 post-hepatectomy in MMP-9 KO mice. MMP-9 KO mice also delayed EGFR activation after PH. STAT3, NF-κB, and cyclinDl, as downstream factors of EGFR, were assessed by Western Blot, which demonstrated that expressions of these molecules were similar to EGFR activation after PH.Conclusions: Our data provide new evidence supporting a critical role of MMP-9 in liver regeneration after PH through activation of EGFR signaling.