title: Matrix metalloprotease 9 promotes liver recovery from ischemia and reperfusion injury.
abstract: BACKGROUND
  Matrix metalloprotease (MMP) 9 has been always considered as a destructor of extracellular matrix, promoting liver injury and metastasis of carcinoma. In this study, we investigated the role of MMP-9 in liver wound healing from ischemia and reperfusion injury (IRI).
  
  
  METHODS
  MMP9-/- mice were used to establish partial hepatic IRI model. Serum alanine aminotransferase and hepatic cytokines (tumor necrosis factor alpha, interleukin [IL]-1β, IL-10, and transforming growth factor beta [TGF-β]) levels were analyzed after IRI. Hepatic stellate cells were isolated from wild-type mice to determine the effect of MMP-9 on TGF-β activation. In addition, the effect of TGF-β on liver wound healing from IRI was determined.
  
  
  RESULTS
  Liver recovery from IRI was impaired in MMP9-/- mice, which was described as elevated serum alanine aminotransferase, hepatic tumor necrosis factor alpha, and IL-1β levels. Meanwhile, TGF-β-active protein level was decreased in the liver of MMP9-/- mice. In vitro test, the activation of TGF-β was suppressed in the presence of anti-MMP-9 monoclonal antibody. TGF-β treatment promoted liver recovery from IRI in MMP9-/- mice.
  
  
  CONCLUSIONS
  MMP-9 promoted liver recovery from IRI by activating TGF-β. Thus, MMP-9 plays dual roles (bad and good) in liver IRI, depending on the timing.
authors.affiliation: Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Quanrongzi
authors.initials: Q
authors.lastname: Wang
authors.forename: Wenxian
authors.initials: W
authors.lastname: Guan
mesh_terms: D000818:Animals; D007511:Ischemia / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000503:physiopathology*; D012097:Repressor Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing
chemical_list: C472089:Mxd3 protein, mouse; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse