Comprehensive analysis of the mechanism of P. gingivalis-promoted NASH-related HCC

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18478
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Meikai University (2022); Hiroshima University (2020-2021)
• Principal Investigator: SAKAMOTO Shinnichi 明海大学, 歯学部, 助教 (60848084)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Porphyromonas gingivalis / NASH関連肝癌 / 酸化ストレス / hCLSs / TNF-α / 8-OHdG

Outline of Final Research Achievements

Transcriptome analysis of non-neoplastic liver tissues from HFD-P.g.(+) and HFD-P.g.(-) groups, in which mice were fed a high-fat diet and P.g. was infected odontogenically for 60 weeks, was conducted. In HFD-P.g.(+) group, macrophage marker (Lyz2) was elevated. Immunohistochemically, HFD-P.g.(+) group showed a significant increase in 8-OHdG, an oxydative DNA damage marker. Previously, we confirmed the increase of hCLSs positive for TNF-α (an inducer of ROS) in HFD-P.g.(+) group. These results suggest that upregulated TNF-α production via hCLSs induced by P.g. infection causes increased oxidative DNA damage, which plays an important role in promoting the process of hepatocarcinogenesis of NASH-related HCC mouse model.

Free Research Field

歯周病と全身疾患

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌は世界で５番目に多い癌であり、癌関連死の２番目を占める。治療法の進歩により減少傾向にあるHCVやHBVによるウイルス発癌と比較し、肥満を契機として生じるNASH関連肝癌は急速に増加している。NASH 関連肝癌の発症・進行メカニズムは未だ不明な点が多い。本研究では、P.g.歯性感染によりNASH関連肝癌マウスモデルの発癌過程が促進される機序として、hCLSsから産生されるTNF-αによる肝細胞の酸化的DNA傷害の関与が示唆された。歯科的介入による歯周病原細菌のコントロールが、NASH関連肝癌発生予防に有用となる可能性が示唆された点で、本研究の学術的意義は大きい。