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Digestive Diseases and Sciences

, Volume 50, Issue 5, pp 942–948 | Cite as

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

  • Keishi Kanno
  • Susumu TazumaEmail author
  • Tomoji Nishioka
  • Hideyuki Hyogo
  • Kazuaki Chayama
Article

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.

Key Words

renin–angiotensin system monocyte chemoattractant protein-1 hepatic stellate cell hepatic inflammation hepatic fibrosis angiotensin II type 1a knockout mouse small G protein Rho/Rho-kinase pathway carbon tetrachloride 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Keishi Kanno
    • 1
  • Susumu Tazuma
    • 2
    • 3
    Email author
  • Tomoji Nishioka
    • 1
  • Hideyuki Hyogo
    • 2
  • Kazuaki Chayama
    • 1
  1. 1.Department of Medicine and Molecular Science, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Division of General MedicineHiroshima University Medical HospitalHiroshimaJapan
  3. 3.Division of General MedicineHiroshima University Medical HospitalHiroshimaJapan

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