Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown etiology that impacts various organs including liver. Recently, human parvovirus B19 (B19) is recognized to exacerbate SLE. However, the effects of B19 on liver in SLE are still unclear. Herein we aimed to investigate the effects of B19 on liver in NZB/W F1 mice by injecting subcutaneously with PBS, recombinant B19 NS1, VP1u or VP2, respectively. Our experimental results revealed that B19 NS1 protein significantly enhanced the TGF-β/Smad fibrotic signaling by increasing the expressions of TGF-β, Smad2/3, phosphorylated Smad2/3, Smad4 and Sp1. The consequent fibrosis-related proteins, PAI-1 and α-SMA, were also significantly induced in livers of NZB/W F1 mice receiving B19 NS1 protein. Accordingly, markedly increased collagen deposition was also observed in livers of NZB/W F1 mice receiving B19 NS1 protein. However, no significant difference was observed in livers of NZB/W F1 mice receiving B19 VP1u or VP2 as compared to the controls. These findings indicate that B19 NS1 plays a crucial role in exacerbating liver fibrosis in NZB/W F1 mice through enhancing the TGF-â/Smad fibrotic signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / metabolism
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Animals
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Collagen / genetics
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Collagen / metabolism
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ErbB Receptors / genetics
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ErbB Receptors / metabolism
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Female
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Humans
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Liver / metabolism
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Liver / pathology*
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Liver / virology
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Liver Cirrhosis / genetics*
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Liver Cirrhosis / metabolism
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Liver Cirrhosis / virology*
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Mice
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Mice, Inbred NZB
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Parvovirus B19, Human / genetics*
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Parvovirus B19, Human / metabolism*
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Phosphorylation / genetics
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Plasminogen Activator Inhibitor 1 / genetics
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Plasminogen Activator Inhibitor 1 / metabolism
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Signal Transduction / genetics
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Smad Proteins / genetics
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Smad Proteins / metabolism
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
Substances
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Actins
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Plasminogen Activator Inhibitor 1
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Smad Proteins
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Transforming Growth Factor beta
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Collagen
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ErbB Receptors
Grants and funding
This study was supported by NSC 97-2314-B040-009, NSC 98–2314-B-040–008-MY3, NSC-99-2320-B-040-004-MY3, NSC 101-2314-B-040-008 and NSC-99-2320- B-040-007-MY3 from the National Science Council, Taiwan, Republic of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.