Direct Contribution of Mitochondorial Oxidative Stress to Hepatic Fibrogenesis

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Oxidative stress is considered to play a key role in the progression of chronic liver diseases. However, since production of oxidative stress may merely represent the consequences of cell damage and subsequent inflammation, it is virtually unknown whether oxidative stress is linked directly to fibrogenesis.Hepatocytes isolated from Tet-mev-1 mouse, in which mitochondrial reactive oxygen species can be induced, exhibited decreased mitochondrial membrane potential. Tet-mev-1 mice were fed high fat/high sucrose (HFHS)diet, and microarray analyses indicated that CC chemokine expression was remarkably elevated in the liver tissue. However, the number of F4/80-positive cells was substantially decreased, and there was noapparent liver fibrosis observed in Tet-mev-1 mice fed HFHS diet. These results suggested the important role of macrophages in the progression of liver fibrosis.