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Mmp-9 deficiency impairs live regeneration through EGFR signaling in partial hepatectomy mice

Bo Zhou;Jianhua Rao;Zhengchao Xu;Guoqiang Li;Xuehao Wang;Ling Lu

  Background:Liver regeneration is a complex process regulated by complex mechanism,relating to cytokine,growth factor,metabolic networks,etc.Previous investigations have demonstrated that Matrix metalloproteinases-9(MMP-9)is an essential factor in liver regeneration after partial hepatectomy,but the correct mechanisms are still unclear.The present study is aimed to explore the role of MMP-9 on epidermal growth factor receptor(EGFR)signaling as well as the related proliferation factors of the signaling in a mouse model of partial hepatectomy(PH).Methods:MMP-9 knockout(KO)and wild-type(WT)mice were used to establish this model.Liver regeneration was first analyzed based on proliferation cell nuclear antigen(PCNA)immunohistochemistry and liver weight to body weight ratio.EGFR ligands,EGFR,and downstream factors were measured after PH.STAT3,NF-κB,and cyclinD1,were assessed by Western Blot.Results:MMP-9 KO mice showed a delayed hepatic regenerative response after PH compared with WT mice.EGFR ligands,including heparin-binding EGF and amphiregulin were significantly lower level expression between days 1 and3 post-hepatectomy in MMP-9 KO mice compared with WT controls.In addition,MMP-9 KO also inhibited and delayed EGFR activation after PH.STAT3,NF-kB,and cyclinDl displayed expressions of these molecules were in line with EGFR activation after PH.Conclusions:Our data provides new evidence to support the critical role of MMP-9 in liver regeneration after PH through activation of EGFR signaling.……   
[关键词]:MMP-9;Liver regeneration;EGFR
[文献类型]:会议论文
[文献出处]: 《第九届全国免疫学学术大会论文集2014年