The mechanism of liver carcinogenesis in NASH from the view point of organ crosstalk using tissue specific conditional rescue mice
Description: We generated p62 and Nrf2 double knockout (DKO) mice and demonstrated that these mice developed to NASH. And, we found that DKO mice developed severe fibrosis and liver cancer induced by high fat diet. To elucidate the mechanism of liver carcinogenesis in organ crosstalk, we generated tissue specific conditional p62 rescue mice. The rescue of hepatocytes p62 suppressed the development of NASH and reduced the prevalence of liver cancer from 39% to 14%.To evaluate the role of p62 in human NASH and liver cancer, clinical specimens collected by surgery were analyzed by p62 immunohistochemistry. The intensity and lorcalization of p62 associated with hepatic inflammation and fibrosis in non-tumor area, however, did not associate with differentiation and size of liver cancers. p62 in hepatocytes played a protective role against the development of steatohepatitis and liver cancer. Activation of p62 could be a promising target for the prevention and treatment of NASH and liver cancer.
Amount: ¥4,420,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2018-04-01
End date: 2021-03-31
Investigator: Kosuke OKADA
Institution: University of Tsukuba
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 5
Funder award ID: 18K07930
OpenAlex ID: G2282136149