Elucidation of interstitial reactions mediated by Nrf2 addiction in pancreaticobiliary maljunction

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08671
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: MORI Hiroki 徳島大学, 病院, 特任助教 (70448330)
• Co-Investigator(Kenkyū-buntansha): 石橋 広樹 徳島大学, 大学院医歯薬学研究部(医学域), 講師 (20314867) ; 山下 祥子 徳島大学, 病院, 特任助教 (20825195) ; 森根 裕二 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60398021)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵・胆管合流異常 / 発がん / Inflammasome / macrophage / fibroblast

Outline of Final Research Achievements

In this study, we focused on the interaction between gallbladder epithelium and interstitial fibroblasts and immunocompetent cells in the chronic inflammation-related carcinogenic mechanism of pancreaticobiliary maljunction. We investigated its involvement in carcinogenesis and found that activated fibroblast and M2 macrophage were increased in the stroma, and NLRP3 expression was increased in both the epithelium and stroma. In addition, NLRP3-positive stromal cells were distributed directly under the NLRP3-positive epithelium. Our results confirmed that NLRP3 expression is increased in the activated fibroblasts of the gallbladder epithelium and stroma in patients with abnormal confluence, and suggested the interaction mediated by activation of NLRP3 in the stroma and epithelium might be involved in carcinogenesis in patients with pancreaticobiliary maljunction.

Free Research Field

消化器外科、小児外科、膵・胆管合流異常、発がん、間質

Academic Significance and Societal Importance of the Research Achievements

発がんポテンシャルを有している膵・胆管合流異常において、上皮細胞と間質の線維芽細胞・免疫担当細胞とのinteractionに焦点を当てたNrf2 addictionを介したNLRP3 Inflammasome活性化の胆道癌発癌への関与を検討することにより、合流異常における胆嚢上皮と間質のActivated fibroblastでのNLRP3発現の上昇が確認でき、間質と上皮のNLRP3の活性化を介したinteractionが合流異常における癌発生に関与する可能性が示唆された。この結果を踏まえて、合流異常の胆道上皮細胞-間質interactionによる更なる発癌機序解明や発癌制御法の開発を目指す。