Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells.
dc.contributor.author | Saeed, A | |
dc.contributor.author | Baloch, K | |
dc.contributor.author | Brown, R J P | |
dc.contributor.author | Wallis, R | |
dc.contributor.author | Chen, L | |
dc.contributor.author | Dexter, L | |
dc.contributor.author | McClure, C P | |
dc.contributor.author | Shakesheff, K | |
dc.contributor.author | Thomson, B J | |
dc.date.accessioned | 2013-11-18T14:13:32Z | |
dc.date.available | 2013-11-18T14:13:32Z | |
dc.date.issued | 2013-11 | |
dc.identifier.citation | Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells. 2013, 174 (2):265-73 Clin. Exp. Immunol. | en |
dc.identifier.issn | 1365-2249 | |
dc.identifier.pmid | 23841802 | |
dc.identifier.doi | 10.1111/cei.12174 | |
dc.identifier.uri | http://hdl.handle.net/10033/305492 | |
dc.description.abstract | Mannan binding lectin (MBL)-associated serine protease type 1 (MASP-1) has a central role in the lectin pathway of complement activation and is required for the formation of C3 convertase. The activity of MASP-1 in the peripheral blood has been identified previously as a highly significant predictor of the severity of liver fibrosis in hepatitis C virus (HCV) infection, but not in liver disease of other aetiologies. In this study we tested the hypotheses that expression of MASP-1 may promote disease progression in HCV disease by direct activation of hepatic stellate cells (HSCs) and may additionally be up-regulated by HCV. In order to do so, we utilized a model for the maintenance of primary human HSC in the quiescent state by culture on basement membrane substrate prior to stimulation. In comparison to controls, recombinant MASP-1 stimulated quiescent human HSCs to differentiate to the activated state as assessed by both morphology and up-regulation of HSC activation markers α-smooth muscle actin and tissue inhibitor of metalloproteinase 1. Further, the expression of MASP-1 was up-regulated significantly by HCV infection in hepatocyte cell lines. These observations suggest a new role for MASP-1 and provide a possible mechanistic link between high levels of MASP-1 and the severity of disease in HCV infection. Taken together with previous clinical observations, our new findings suggest that the balance of MASP-1 activity may be proinflammatory and act to accelerate fibrosis progression in HCV liver disease. | |
dc.language.iso | en | en |
dc.rights | Archived with thanks to Clinical and experimental immunology | en |
dc.title | Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells. | en |
dc.type | Article | en |
dc.contributor.department | School of Molecular Medical Sciences, University of Nottingham, Leicester, UK; School of Pharmacy, University of Nottingham, Leicester, UK. | en |
dc.identifier.journal | Clinical and experimental immunology | en |
refterms.dateFOA | 2014-11-15T00:00:00Z | |
html.description.abstract | Mannan binding lectin (MBL)-associated serine protease type 1 (MASP-1) has a central role in the lectin pathway of complement activation and is required for the formation of C3 convertase. The activity of MASP-1 in the peripheral blood has been identified previously as a highly significant predictor of the severity of liver fibrosis in hepatitis C virus (HCV) infection, but not in liver disease of other aetiologies. In this study we tested the hypotheses that expression of MASP-1 may promote disease progression in HCV disease by direct activation of hepatic stellate cells (HSCs) and may additionally be up-regulated by HCV. In order to do so, we utilized a model for the maintenance of primary human HSC in the quiescent state by culture on basement membrane substrate prior to stimulation. In comparison to controls, recombinant MASP-1 stimulated quiescent human HSCs to differentiate to the activated state as assessed by both morphology and up-regulation of HSC activation markers α-smooth muscle actin and tissue inhibitor of metalloproteinase 1. Further, the expression of MASP-1 was up-regulated significantly by HCV infection in hepatocyte cell lines. These observations suggest a new role for MASP-1 and provide a possible mechanistic link between high levels of MASP-1 and the severity of disease in HCV infection. Taken together with previous clinical observations, our new findings suggest that the balance of MASP-1 activity may be proinflammatory and act to accelerate fibrosis progression in HCV liver disease. |