| セッション情報 | The 8th JSGE-AGA Joint Meeting |
|---|---|
| タイトル | JM-2：The Role of Hepatic Stellate Cells in Fibrogenesis |
| 演者 | Kawada Norifumi（Department of Hepatology, Graduate School of Medicine, Osaka City University, Japan） |
| 共同演者 | |
| 抄録 | Molecular analysis of hepatic fibrogenesis has progressed with respect to both fibrosis progression and regression by using cell biological, molecular biological, and（epi）genetic approaches. Recent researches have revealed sources of collagen-producing cells other than hepatic stellate cells in the liver, and the involvement of the innate immune system and oxidative stress in the fibrotic process has attracted new attention with regard to hepatic carcinogenesis. Previously, we identified cytoglobin（Cygb）from rat hepatic stellate cells by using proteomics approach. Human Cygb has about 25% amino acid identity with vertebrate myoglobin and hemoglobin. Unlike myoglobin, which is tissue restricted to cardiomyocytes and skeletal myofibers, hemoglobin in erythrocytes, and neuroglobin in nervous system, Cygb is ubiquitously expressed in the cytoplasm of mesenchymal pericytes of many kinds of organs. Cygb may facilitate diffusion of oxygen through tissues, scavenge nitric oxide or other reactive oxygen species, or serve a protective function during oxidative stress. To clarify the molecular function of Cygb in vivo, we generated Cygb knockout mice and investigated N, N-diethylnitrosamine（DEN）-induced tumorigenesis using these mice. Cygb deficiency obviously promoted DEN-induced development of liver tumors. Cygb loss was associated with increased cancer cell proliferation, elevated Erk and Akt activation, overexpression of IL-1β, IL-6, TNFα, and TGFβ3 mRNAs, and hepatic collagen accumulation. Cygb-deficient mice also exhibited increased nitrotyrosine formation and dysregulated expression of genes related to the pathway in cancer. These results strongly suggested that Cygb deficiency induced susceptibility to cancer development in the liver of mice under DEN treatment. Globins such as Cygb will shed a new light on the biology of organ carcinogenesis. |
| 索引用語 |