Elucidation of role of tissue or cellular Nrf2 in regulating NASH onset and progression using genetically modified mice.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26282191
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: University of Tsukuba
• Principal Investigator: SHODA JUNICHI 筑波大学, 医学医療系, 教授 (90241827)
• Co-Investigator(Kenkyū-buntansha): 柳川 徹 筑波大学, 医学医療系, 准教授 (10312852) ; 酒井 俊 筑波大学, 医学医療系, 講師 (30282362) ; 磯辺 智範 筑波大学, 医学医療系, 准教授 (70383643) ; 蕨 栄治 筑波大学, 医学医療系, 講師 (70396612)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肥満 / 脂肪性肝炎 / 転写因子 / 酸化ストレス / エンドトキシン / 遺伝子改変マウス

Outline of Final Research Achievements

p62:Nrf2 double knockout mice (DKO) fed with normal diet develop spontaneous NASH in association with mature-onset hyperphagic obesity. Therefore, to elucidate the onset mechanism of NASH, we focused interests on the intestines and Kupffer cells. In the analysis of intestinal microflora, the number of gram-negative bacteria species was increased in DKO and the serum and fecal LPS concentrations were also increased. The intestinal permeability was increased in Nrf2-KO mice and DKO. The inflammatory cytokine production was increased in the Kupffer cells. It is likely that the onset mechanism of NASH is attributed to an increase in gram-negative bacteria species due to p62 deficiency and a weakness of intestinal barrier function due to Nrf2 defeciency, which in turn let an increased influx of LPS into the liver.

Free Research Field

肝臓病学