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Publication : Matrix metalloprotease 9 promotes liver recovery from ischemia and reperfusion injury.

First Author  Feng M Year  2013
Journal  J Surg Res Volume  180
Issue  1 Pages  156-61
PubMed ID  23157925 Mgi Jnum  J:302750
Mgi Id  MGI:6509691 Doi  10.1016/j.jss.2012.09.042
Citation  Feng M, et al. (2013) Matrix metalloprotease 9 promotes liver recovery from ischemia and reperfusion injury. J Surg Res 180(1):156-61
abstractText  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]-1beta, IL-10, and transforming growth factor beta [TGF-beta]) levels were analyzed after IRI. Hepatic stellate cells were isolated from wild-type mice to determine the effect of MMP-9 on TGF-beta activation. In addition, the effect of TGF-beta 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-1beta levels. Meanwhile, TGF-beta-active protein level was decreased in the liver of MMP9-/- mice. In vitro test, the activation of TGF-beta was suppressed in the presence of anti-MMP-9 monoclonal antibody. TGF-beta treatment promoted liver recovery from IRI in MMP9-/- mice. CONCLUSIONS: MMP-9 promoted liver recovery from IRI by activating TGF-beta. Thus, MMP-9 plays dual roles (bad and good) in liver IRI, depending on the timing.
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