Understanding the intestinal homeostasis from the perspective of ubiquitin modification

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H04024
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Fukushima Medical University (2019-2020); Tokyo Medical and Dental University (2017-2018)
• Principal Investigator: Onizawa Michio 福島県立医科大学, 医学部, 助教 (30783352)
• Co-Investigator(Kenkyū-buntansha): 渡辺 守 東京医科歯科大学, 高等研究院, 特別栄誉教授 (10175127)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 炎症性腸疾患

Outline of Final Research Achievements

It is thought that environmental factors such as intestinal microflora and diet play critical roles in the development of inflammatory bowel disease. However, it is little known as to what kind of environmental factors are involved in this disease and how these factors affect the intestinal homeostasis. We observed that more proteins are ubiquitinated in the large intestine of germ free mice than in that of specific pathogen free mice. We showed that mass spectrometric analysis enables comprehensive identification of ubiquitinated proteins in the colon. We also found that oral administration of D-serine, not L-serine, has a preventive and therapeutic effect in a naive T cell transfer model of chronic colitis.

Free Research Field

消化管

Academic Significance and Societal Importance of the Research Achievements

生体環境による組織のモニタリング手法としてトランスクリプトーム解析が一般的であるが、本研究により、組織の網羅的ユビキチン化修飾解析技術も有用であること示した。また、IBDとDアミノ酸の関連は不明であったが、DセリンがIBDモデルを抑制することを示した本研究結果は、IBDにおけるDアミノ酸研究発展の必要性を示している。合わせて本研究成果は、DセリンによるIBDの画期的な予防法・新規治療法の開発の基盤になり得ると思われる。