The role of gap junctional intercellular communication in NASH and its-related hepatocarcinogenesis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagoya City University
• Principal Investigator: NAIKI-ITO Aya 名古屋市立大学, 大学院医学研究科, 講師 (20509236)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: NASH / 細胞間コミュニケーション / 疾患モデル / フラボノイド / 肝発がん

Outline of Final Research Achievements

NASH has the potential to lead to the development of cirrhosis and hepatocellular carcinoma (HCC). To clarify the role of hepatocyte gap junction protein, Cx32 and luteolin on the progression of NASH and hepatocarcinogenesis, Cx32 dominant negative transgenic (Tg) were used. Steatohepatitis, fibrosis, inflammatory cytokine expression, reactive oxygen species and number of preneoplastic foci were greater in Tg as compared with Wt rats, and significantly suppressed by luteolin in both genotypes. Microarray analysis identified Bex1 as an up-regulated gene in Tg rat liver. in situ hybridization revealed that increased Bex1 mRNA was localized in preneoplastic foci in Tg rats. Moreover, Bex1 increased cell proliferation through activation of NF-κB signaling in rat hepatocyte and HCC cell lines. These results show that Cx32 and luteolin have suppressive roles in inflammation, fibrosis and hepatocarcinogenesis during NASH progression, suggesting a potential therapeutic application for NASH.

Free Research Field

発がん