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2021 Fiscal Year Final Research Report

Roles of DAMP and autophagy in inflammation-related carcinogenesis and its application to cancer prevention

Research Project

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Project/Area Number 19H03884
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 58020:Hygiene and public health-related: including laboratory approach
Research InstitutionMie University

Principal Investigator

MURATA Mariko  三重大学, 医学系研究科, 教授 (10171141)

Co-Investigator(Kenkyū-buntansha) 及川 伸二  三重大学, 医学系研究科, 准教授 (10277006)
翠川 薫  鈴鹿大学, こども教育学部, 教授 (20393366)
有馬 寧  鈴鹿医療科学大学, 医療科学研究科, 教授 (30263015)
Project Period (FY) 2019-04-01 – 2022-03-31
Keywordsがん / 炎症 / 傷害関連分子パターン / アポトーシス / オートファジー / DNA損傷
Outline of Final Research Achievements

DNA damage and damage-associated molecular patterns (DAMPs) released from damaged cells are important for inflammation-related cancer progression. We found that a representative DAMP, nuclear protein HMGB1, was associated with cancer distant metastasis status in liver fluke-infested cholangiocarcinoma patients when it translocates from the nucleus to the cytoplasm. Glycyrrhizin, an HMGB1 inhibitor, reduced the number of colorectal tumors and suppressed inflammation-related molecules in a mouse model of ulcerative colitis-colorectal cancer. In a nude mouse xenograft of subcutaneously implanted nasopharyngeal carcinoma cells, taurine significantly reduced tumor weight and increased expression of apoptosis- and autophagy-related molecules. These results suggest the potential of chemopreventive agents in inflammation-related carcinogenesis.

Free Research Field

環境分子医学

Academic Significance and Societal Importance of the Research Achievements

感染や炎症は、発がん要因の約25%を占めると推察され、その機構の解明と予防方法の探索は社会的課題である。我々は、インジウム化合物による健康障害が、HMGB1-RAGE-TLR9経路を介した肺上皮での炎症とDNA損傷が関与する可能性を示した。また、HMGB1が核から細胞質へ移行する、あるいは細胞外へ放出されることが炎症を増強させ、更なる遺伝子損傷の蓄積という悪循環に陥り、がんの進展に繋がることを見出した。グリチルリチンのHMGB1阻害作用により、潰瘍性大腸炎-大腸がんモデルマウスにおいて、がんの抑制が認められたことは、炎症関連発がんにおけるHMGB1の重要性を示すものであり、学術的意義は高い。

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Published: 2023-01-30  

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