Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in mice fed high-fat diet
Autor: | Yi Chen, Yasunori Okada, Naoto Fukuyama, Hiroe Nakazawa, Chizuko Tsuji, Tetsuya Mine, Shinkichi Sato, Yoichi Ogushi, Shigenari Hozawa, Sadaaki Sawamura, Ryuzaburo Tanino |
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Rok vydání: | 2004 |
Předmět: |
Liver Cirrhosis
medicine.medical_specialty Gelatin Zymography Biophysics Nitric Oxide Synthase Type II Severity of Illness Index Biochemistry Mice chemistry.chemical_compound Fibrosis Internal medicine medicine Animals Zymography Molecular Biology Mice Knockout biology Chemistry Nitrotyrosine Cell Biology medicine.disease Dietary Fats Matrix Metalloproteinases Fatty Liver Mice Inbred C57BL Nitric oxide synthase Endocrinology Liver Knockout mouse biology.protein Nitric Oxide Synthase Steatohepatitis Hepatic fibrosis Procollagen |
Zdroj: | Biochemical and Biophysical Research Communications. 326:45-51 |
ISSN: | 0006-291X |
DOI: | 10.1016/j.bbrc.2004.10.202 |
Popis: | 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. |
Databáze: | OpenAIRE |
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