Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells

Saeed, A. ORCID: https://orcid.org/0000-0003-2903-5875, Baloch, K., Brown, R. J. P., Wallis, R., Chen, L., Dexter, L., Mcclure, C. P., Shakesheff, K. and Thomson, B. J. (2013) Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells. Clinical and Experimental Immunology, 174 (2). pp. 265-273. ISSN 0009-9104

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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.

Item Type:	Article
Uncontrolled Keywords:	fibrosis,hepatitis c,innate immune response,masp-1,immunology and allergy,immunology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2723
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	10 Jul 2021 00:06
Last Modified:	25 Sep 2024 15:41
URI:	https://ueaeprints.uea.ac.uk/id/eprint/80518
DOI:	10.1111/cei.12174

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