These data suggest that exploring the metabolism of retinoids in liver diseases and their target genes provides us with useful information to understand the liver functions Fulvestrant clinical trial and diseases. Consequently, the altered metabolism of retinoids was observed in liver diseases, including non-alcoholic fatty liver disease. In this review, we summarize the metabolism of retinoids in the liver, highlight the functions of retinoids in HCC,

non-alcoholic fatty liver disease, and alcoholic liver disease, and discuss the target genes of RA. Investigation of retinoids in the liver will likely help us identify novel therapies and diagnostic modalities for HCC. Hepatocellular carcinoma (HCC) is the third most common cancer and is reportedly increasing worldwide.[1] Prognosis

of HCC patients has improved due to the progress of local therapies of HCC. However, biological features of HCC result in high rates of secondary occurrence GSK126 mw of HCC after the successful treatment of primary tumor. Therefore, novel therapies are required to suppress malignant potential of HCC. The major cause of HCC is hepatitis C virus (HCV) in Western countries. In Japan, 80% of HCC patients have HCV as a cause of cancer. The occurrence of HCC is caused by direct or indirect effects of HCV core protein. The direct effects of HCV core protein on the development and progression of HCC include production of reactive oxygen species (ROS), and altered signal transduction of mitogen-activated protein kinases such as JNK, p38, and ERK1/2.[2] The indirect effects

of HCV core protein include abnormal turnover rate of hepatocyte death and regeneration, which is due to the oxidative stress Ibrutinib concentration generated by HCV, leading to DNA damage and mutation. In addition, activation of hepatic stellate cells (HSCs), which migrate along the space of Disse between hepatocytes and endothelial cells, indirectly promotes HCC occurrence.[3] As demonstrated in experimental animal models, activation of HSCs induces overproduction of transforming growth factor-β and platelet-derived growth factor, which promote HCC.[4, 5] In addition, HSC activation and the progression of liver diseases are associated with the loss of lipid droplets containing vitamin A.[6, 7] Since epidemiological data suggest that vitamin A acts as an inhibitor of carcinogenesis in several organs, including stomach, breast, lung, prostate, and liver,[8-12] we propose the hypothesis that the loss of vitamin A in HSCs is a contributing factor in the progression of HCC. Importantly, hepatitis B surface antigen-positive individuals with lower serum retinol concentrations have sevenfold higher risk of HCC compared with those with higher serum retinol concentrations,[12] suggesting that reduced retinol content is a high risk factor of HCC.