ArticleWorld journal of gastroenterology2013
Matrix metalloproteinase-9 in the initial injury after hepatectomy in mice.
Article in World journal of gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 12 citations in OpenAlex.
- Article
- Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced Chronic Hepatitis and Progression to Cirrhosis.Frontiers in immunology · 2017Review
- Nitro-oxidative stress, VEGF and MMP-9 in patients with cirrhotic and non-cirrhotic portal hypertension.Clujul medical (1957) · 2015Article
- Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats.World journal of hepatology · 2014Article
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
aimTo investigate the role of matrix metalloproteinase (MMP)-9 in the pathogenesis of postoperative liver failure (PLF) after extended hepatectomy (EH).
methodsAn insufficient volume of the remnant liver (RL) results in higher morbidity and mortality, and a murine model with 80%-hepatectomy was used. All investigations were performed 6 h after EH. Mice were first divided into two groups based on the postoperative course (i.e., the PLF caused or did not), and MMP-9 expression was measured by Western blotting. The source of MMP-9 was then determined by immunohistological stainings. Tissue inhibitor of metalloproteinase (TIMP)-1 is the endogenous inhibitor of MMP-9, and MMP-9 behavior was assessed by the experiments in wild-type, MMP-9(-/-) and TIMP-1(-/-) mice by Western blotting and gelatin zymography. The behavior of neutrophils was also assessed by immunohistological stainings. An anti-MMP-9 monoclonal antibody and a broad-spectrum MMP inhibitor were used to examine the role of MMP-9.
resultsSymptomatic mice showed more severe PLF (histopathological assessments: 2.97 ± 0.92 vs 0.11 ± 0.08, P < 0.05) and a higher expression of MMP-9 (71085 ± 18274 vs 192856 ± 22263, P < 0.01). Nonnative leukocytes appeared to be the main source of MMP-9, because MMP-9 expression corresponding with CD11b positive-cell was observed in the findings of immunohistological stainings. In the histopathological findings, the PLF was improved in MMP-9(-/-) mice (1.65% ± 0.23% vs 0.65% ± 0.19%, P < 0.01) and it was worse in TIMP-1(-/-) mice (1.65% ± 0.23% vs 1.78% ± 0.31%, P < 0.01). Moreover, neutrophil migration was disturbed in MMP-9(-/-) mice in the immunohistological stainings. Two methods of MMP-9 inhibition revealed reduced PLF, and neutrophil migration was strongly disturbed in MMP-9-blocked mice in the histopathological assessments (9.6 ± 1.9 vs 4.2 ± 1.2, P < 0.05, and 9.9 ± 1.5 vs 5.7 ± 1.1, P < 0.05).
conclusionMMP-9 is important for the process of PLF. The initial injury is associated with MMP-9 derived from neutrophils, and MMP-9 blockade reduces PLF. MMP-9 may be a potential target to prevent PLF after EH and to overcome an insufficient RL.
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