The ER stress preconditioning as a therapeutic strategy for NSAIDs-induced intestinal ulcer.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15765
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Osaka Medical College
• Principal Investigator: Kojima Yuichi 大阪医科大学, 医学部, 特別職務担当教員(講師) (10747744)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: オートファジー / ERストレス

Outline of Final Research Achievements

We aimed to find out therapies to prevent or cure NSAIDs-induced small intestine ulcer. To achieve this, we eventually focused on autophagy induction through experiments in this project. We evaluated effects of various molecules which have been to known to induce autophagy, such as mTOR inhibitor, rapamaycin on IM induced small intestine ulcer, and noticed that these molecules alleviated IM-induced toxicity on rat small intestine epithelial cell line, IEC6 cells in a dose-dependent manner. Among these molecules, a glycolytic pathway inhibitor, X, has induced autophagy as well as autophagy and suppressed cell injury, most efficiently. X has successfully alleviated small intestine ulcer in mouse model with IM. X was already focused as a cancer therapeutics, and we believe that X will be applicable to real-world human therapy.

Free Research Field

小腸傷害

Academic Significance and Societal Importance of the Research Achievements

NSAIDsは、世界中で汎用されている薬物である。代表的な有害作用である胃粘膜傷害は、胃酸分泌阻害薬、あるいは、胃粘膜保護薬で予防、治療可能であるが、未知な点が多い小腸傷害では、未だに確立された治療法は存在しない。オートファジーを標的とした治療は、神経変性疾患、循環器疾患等で注目されており、本研究において、忍容性の高い物質によるオートファジー/ERストレスの人為的な誘導がNSAIDs誘因性小腸傷害治療につながる可能性が示唆されたことは、大きな学術的及び社会的な意義を持つ。