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

Research output: Contribution to journalArticle

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

Fingerprint

High Fat Diet
Nitric Oxide Synthase Type II
Nutrition
Fibrosis
Fats
Liver
Matrix Metalloproteinases
Fatty Liver
Tissue
Gelatin
Liver Cirrhosis

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in mice fed high-fat diet. / Chen, Yi; Hozawa, Shigenari; Sawamura, Sadaaki; Sato, Shinkichi; Fukuyama, Naoto; Tsuji, Chizuko; Mine, Tetsuya; Okada, Yasunori; Tanino, Ryuzaburo; Ogushi, Yoichi; Nakazawa, Hiroe.

In: Biochemical and Biophysical Research Communications, Vol. 326, No. 1, 31.12.2004, p. 45-51.

Research output: Contribution to journalArticle

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, vol. 326, no. 1, pp. 45-51. https://doi.org/10.1016/j.bbrc.2004.10.202
Chen, Yi ; Hozawa, Shigenari ; Sawamura, Sadaaki ; Sato, Shinkichi ; Fukuyama, Naoto ; Tsuji, Chizuko ; Mine, Tetsuya ; Okada, Yasunori ; Tanino, Ryuzaburo ; Ogushi, Yoichi ; Nakazawa, Hiroe. / Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in mice fed high-fat diet. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 326, No. 1. pp. 45-51.
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