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Reactive oxygen species and NADPH oxidase 4 induced by transforming growth factor β1 are the therapeutic targets of polyenylphosphatidylcholine in the suppression of human hepatic stellate cell activation

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Abstract

Objective and design

To clarify the molecular mechanism of polyenylphosphatidylcholine (PPC), we examined the involvement of reactive oxygen species (ROS) and NADPH oxidase 4 (Nox4) in human hepatic stellate cells (HSCs).

Material

Using human LX-2 HSC cells, we examined the effects of PPC on expression of α-smooth muscle actin (α-SMA) and collagen 1, generation of ROS, Nox4 expression, p38 activation and cell proliferation, induced by transforming growth factor β1 (TGFβ1).

Results

PPC suppressed ROS which are induced by TGFβ1, phosphorylation of p38MAPK, and expression levels of α-SMA and collagen 1 in a dose-dependent manner. Higher concentrations of PPC also suppressed Nox4 levels.

Conclusion

These results suggest that ROS and Nox4 induced by TGFβ1 are the therapeutic targets of PPC in the suppression of human hepatic stellate cell activation.

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Abbreviations

PPC:

Polyenylphosphatidylcholine

HSC:

Hepatic stellate cell

Nox:

NADPH oxidase

MFB:

Myofibroblast

PDGF:

Platelet-derived growth factor

TGFβ1:

Transforming growth factor β-1

ECM:

Extracellular matrix

HCC:

Hepatocellular carcinoma

LC:

Liver cirrhosis

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Authors and Affiliations

  1. Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, 683-8504, Japan

    Remina Ikeda, Kyoko Ishii, Yoshiko Hoshikawa, Junya Azumi, Yuta Arakaki, Toshihiro Yasui, Shizuka Matsuura, Yoshiaki Matsumi, Yohei Kono, Yusuke Mizuta, Akihiro Kurimasa & Goshi Shiota

  2. Division of Regenerative Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan

    Ichiro Hisatome

  3. Division of Liver Diseases, Mount Sinai School of Medicine, New York, USA

    Scott L. Friedman

  4. Department of Internal Medicine, San-in Rosai Hospital, Yonago, Japan

    Hironaka Kawasaki

Authors
  1. Remina Ikeda
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  2. Kyoko Ishii
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  3. Yoshiko Hoshikawa
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  4. Junya Azumi
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  5. Yuta Arakaki
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  8. Yoshiaki Matsumi
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  9. Yohei Kono
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  10. Yusuke Mizuta
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  11. Akihiro Kurimasa
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  12. Ichiro Hisatome
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  13. Scott L. Friedman
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  14. Hironaka Kawasaki
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  15. Goshi Shiota
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Corresponding author

Correspondence to Goshi Shiota.

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Responsible Editor: Liwu Li.

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Ikeda, R., Ishii, K., Hoshikawa, Y. et al. Reactive oxygen species and NADPH oxidase 4 induced by transforming growth factor β1 are the therapeutic targets of polyenylphosphatidylcholine in the suppression of human hepatic stellate cell activation. Inflamm. Res. 60, 597–604 (2011). https://doi.org/10.1007/s00011-011-0309-6

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  • DOI: https://doi.org/10.1007/s00011-011-0309-6

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