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Angiotensin II Participates in Hepatic Inflammation and Fibrosis through MCP-1 Expression

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Abstract

In this study, we assessed the hypothesis that angiotensin (Ang) II could modulate inflammatory cell recruitment into the liver through hepatic expression of monocyte chemoattractant protein (MCP)-1 during liver injury. For in vivo study, Ang II type 1a knockout (AT1a KO) mice and wild-type (WT) mice were treated with CCl4 for 4 weeks. After CCl4 treatment, AT1a KO mice showed lower expression of MCP-1 and fewer CD68-positive cells in the liver compared with WT mice. For in vitro study, Ang II was added to LI90 cells. Ang II enhanced MCP-1 mRNA together with RhoA mRNA and also induced secretion of MCP-1 into the culture medium. This change was strongly blocked by Y-27632, a specific Rho-kinase inhibitor. These results suggest that Ang II modulates hepatic inflammation via production of MCP-1 by hepatic stellate cells, and the effect of Ang II on MCP-1 production is, at least partly, mediated by the Rho/Rho-kinase pathway.

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Authors and Affiliations

  1. Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

    Keishi Kanno MD, Tomoji Nishioka MD & Kazuaki Chayama MD

  2. Division of General Medicine, Hiroshima University Medical Hospital, Hiroshima, Japan

    Susumu Tazuma MD & Hideyuki Hyogo MD

  3. Division of General Medicine, Hiroshima University Medical Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Susumu Tazuma MD

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  1. Keishi Kanno MD
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  2. Susumu Tazuma MD
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  3. Tomoji Nishioka MD
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  4. Hideyuki Hyogo MD
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  5. Kazuaki Chayama MD
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Correspondence to Susumu Tazuma MD.

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Kanno, K., Tazuma, S., Nishioka, T. et al. Angiotensin II Participates in Hepatic Inflammation and Fibrosis through MCP-1 Expression. Dig Dis Sci 50, 942–948 (2005). https://doi.org/10.1007/s10620-005-2669-7

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  • DOI: https://doi.org/10.1007/s10620-005-2669-7

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