Min Feng1, Hao Wang, Quanrongzi Wang, Wenxian Guan. 1. Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
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.
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.