Article Text

other Versions

PDF
Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats
  1. Kohji Kinoshita (s_kinoshi_hyo{at}yahoo.co.jp)
  1. Hyogo College of Medicine, Japan
    1. Yuji Iimuro (siimuro{at}hyo-med.ac.jp)
    1. Hyogo College of Medicine, Japan
      1. Kohji Otogawa (tto92029{at}yahoo.co.jp)
      1. Graduate School of Medicine, Osaka City University, Japan
        1. Shizuya Saika (shizuya{at}wakayama-med.ac.jp)
        1. Wakayama Medical University, Japan
          1. Yutaka Inagaki (yutakai{at}is.icc.u-tokai.ac.jp)
          1. Tokai University School of Medicine, Japan
            1. Yuji Nakajima (yuji{at}med.osaka-cu.ac.jp)
            1. Graduate School of Medicine, Osaka City University, Japan
              1. Norifumi Kawada (kawadanori{at}med.osaka-cu.ac.jp)
              1. Graduate School of Medicine, Osaka City University, Japan
                1. Jiro Fujimoto (sfujimo{at}hyo-med.ac.jp)
                1. Hyogo College of Medicine, Japan
                  1. Scott Friedman (scott.friedman{at}mssm.edu)
                  1. Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, United States
                    1. Kazuo Ikeda (ikeda{at}med.osaka-cu.ac.jp)
                    1. Graduate School of Medicine, Osaka City University, Japan

                      Abstract

                      Background: Liver cirrhosis, which is caused by the undesirable accumulation of extracellular matrix materials (ECM), is a serious clinical problem that can progress to severe hepatic failure. Transforming growth factor-β (TGF-β) plays a pivotal role in ECM production during the process. Bone morphogenetic protein (BMP)-7, a member of the TGF-β superfamily, can antagonize the fibrogenic activity of TGF-β.

                      Aim: In this study, we tested whether adenovirus- mediated overexpression of BMP-7 (Ad-BMP-7) antagonized the effect of TGF-β in vitro and in vivo.

                      Methods and Results: In primary-cultured rat stellate cells and the LX-2 human stellate cell line, induction of BMP-7 by Ad-BMP-7 infection decreased the expression of collagen 1A2 mRNA and smooth muscle & [alpha]-actin in the presence or absence of TGF-β, via Smad1/5/8 phosphorylation. BMP-7 triggered the mRNA expression of inhibitors of differentiation 2 (Id2) in LX-2. Although endogenous expression of BMP-7 was hardly detectable, Smad1 and Id2 overexpression increased BMP-7 expression in LX-2. A liver fibrosis model was induced by the repetitive intraperitoneal injection of thioacetamide (200 mg/kg body weight) twice per week for up to 7 weeks. In rats that were received Ad-BMP-7 via tail vein, hydroxyproline content and the areas stained by Sirius red dye in the liver were significantly reduced compared to the controls. Furthermore, Ad-Id2 reduced fibrosis as well.

                      Conclusion: These data demonstrate that BMP-7, Smad1/5/8 and Ids interact reciprocally and antagonize hepatic fibrogenesis.

                      • BMP-7
                      • Id2
                      • TGF- β
                      • hepatic stellate cells
                      • liver fibrosis

                      Statistics from Altmetric.com

                      Request permissions

                      If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

                      Linked Articles

                      • Digest
                        Robin Spiller Emad El-Omar