Analyses of the effects of hypoxia on the progression of liver disease and hepatic carcinogenesis.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461000
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyushu University
• Principal Investigator: Kato Masaki 九州大学, 大学病院, 助教 (60444808)
• Co-Investigator(Kenkyū-buntansha): Kotoh Kazuhiro 九州大学, 大学病院, 講師 (80289579)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 低酸素 / 肝線維化 / 肝発癌 / 肝星細胞 / 末梢血単核球 / indian hedgehog / adrenomedullin / p21

Outline of Final Research Achievements

Intrahepatic hypoxia may enhance liver fibrosis and stimulate hepatic carcinogenesis in chronic liver disease. In thioacetamide induced rat chronic liver injury model, we observed the presence of hypoxia in liver parenchyma in the early period of injury and the activation of hepatic stellate cell, probably due to the down-regulation of Indian hedgehog. Then we analyzed the mRNA expression levels of hypoxia responsible genes in the peripheral blood mononuclear cells isolated from the patients with chronic liver disease. We observed the enhanced expressions of hypoxia response genes (HIF1, HO-1), and angiogenesis regulating genes (VEGFA, Adrenomedullin), which may suggest the presence of intrahepatic hypoxia. Corresponding expression of p21, a gene sensitive to DNA injury, was also elevated, suggesting the intrahepatic hypoxia may be involved in the DNA injury, leading to the increase of the risk of liver cancer.

Free Research Field

肝臓病学