Research Project
Grant-in-Aid for Research Activity Start-up
This study analyzed the mechanisms of NASH- and obesity-associated hepatocarcinogenesis using new mouse models. Feeding an HFD to MUP-uPA mice resulted in steatohepatitis that closely resembles the pathology of human NASH, eventually leading to spontaneous development of HCC. In this mouse model, the vicious cycle of ER stress and hypernutrition synergistically aggravates lipid accumulation in the liver via SREBP activation, which leads to excess oxidative stress, ballooning degeneration, and susceptibility to lipotoxic cell death. In parallel, increased TNFα expression during this process further accelerates NASH and HCC development in a TNF receptor 1-IKK-NF-κB-dependent manner. Reducing ER stress using chemical chaperones significantly improved liver pathology, suggesting that interrupting this vicious cycle might be a promising therapeutic target for NASH and HCC.
All 2015 2014 Other
All Journal Article (3 results) (of which Peer Reviewed: 3 results, Open Access: 1 results) Presentation (2 results)
J Gastroenterol Hepatol.
Volume: 30 Issue: 2 Pages: 379-88
10.1111/jgh.12719
Cancer Cell
Volume: 26 Issue: 3 Pages: 331-343
10.1016/j.ccr.2014.07.001
Proc Natl Acad Sci U S A.
Volume: 111 Issue: 3 Pages: 1090-1095
10.1073/pnas.1322731111
