Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in mice fed high-fat diet

Yi Chen, Shigenari Hozawa, Sadaaki Sawamura, Shinkichi Sato, Naoto Fukuyama, Chizuko Tsuji, Tetsuya Mine, Yasunori Okada, Ryuzaburo Tanino, Yoichi Ogushi, Hiroe Nakazawa

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41 Citations (Scopus)

Abstract

The role of inducible nitric oxide synthase (iNOS) in the progression of fibrosis during nonalcoholic steatohepatitis remains to be elucidated. This study examined the role of iNOS in the progression of fibrosis during steatohepatitis by comparing iNOS knockout (iNOS -/-) and wild-type (iNOS +/+) mice that were fed a high-fat diet. Severe fatty metamorphosis developed in the liver of iNOS +/+ and iNOS -/- mice. Fibrotic changes were marked in iNOS -/- mice. Gelatin zymography showed that pro MMP-2 and pro MMP-9 protein expressions were more highly induced in iNOS +/+ mice than in iNOS -/- mice. Active forms of MMP-2 and MMP-9 were clearly present only in the liver tissue of iNOS +/+ mice. In situ zymography showed strong gelatinolytic activities in the liver tissue of iNOS +/+ mice, but only spotty activity in iNOS -/-mice. iNOS may attenuate the progression of liver fibrosis in steatohepatitis, in part by inducing MMP-2 and MMP-9 expression and augmenting their activity.

Original languageEnglish
Pages (from-to)45-51
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume326
Issue number1
DOIs
Publication statusPublished - 2004 Dec 31
Externally publishedYes

Keywords

  • Inducible nitric oxide
  • Knockout mice
  • Nitrotyrosine
  • Steatohepatitis
  • Zymography

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Chen, Y., Hozawa, S., Sawamura, S., Sato, S., Fukuyama, N., Tsuji, C., Mine, T., Okada, Y., Tanino, R., Ogushi, Y., & Nakazawa, H. (2004). Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in mice fed high-fat diet. Biochemical and Biophysical Research Communications, 326(1), 45-51. https://doi.org/10.1016/j.bbrc.2004.10.202