Role of caspase-11 and pyroptosis in intestinal ischemia-reperfusion injury

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16457
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Jichi Medical University
• Principal Investigator: Ito Homare 自治医科大学, 医学部, 助教 (60625573)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: インフラマソーム / 炎症 / サイトカイン / 細胞死 / 消化器疾患

Outline of Final Research Achievements

Intestinal ischemia/reperfusion (I/R) injury causes intestinal injury and leads to inflammation and remote organ injury; however, the mechanism of intestinal I/R injury remains unclear. Here, we investigated the role of caspase-11 (Casp11) and gasdermin D (GSDMD)-mediated pyroptosis in intestinal I/R injury. Missense mutation of Casp11 markedly prolonged survival after intestinal I/R injury. Western blot analysis showed that GSDMD was expressed in various organs. Notably, the expression of GSDMD-NT (N-terminal fragment) was detected in the small intestine, indicating the activation of intestinal GSDMD. The expression of GSDME was also detected in the small intestine. These findings suggest the role of Casp11, GSDMD, and GSDME in the pathophysiology of intestinal I/R injury.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、腸管I/R障害においてCasp11およびGSDMD/GSDMEを介したPyroptosisが重要な役割を果たしていることが示された。今後の研究の発展により、腸管I/R障害の新たな分子機序の解明や新規治療法の手がかりが得られることが期待される。