In toto understanding of organ function by integrated analysis of multicellular networks mediated by intercellular delivery of metabolites

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H06270
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Single-year Grants
• Research Field: General internal medicine and related fields
• Research Institution: Keio University
• Principal Investigator: ITOH Hiroshi 慶應義塾大学, 医学部(信濃町), 教授 (40252457)
• Co-Investigator(Kenkyū-buntansha): 宮下 和季 慶應義塾大学, 医学部(信濃町), 特任准教授 (50378759)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 代謝産物 / 液性因子 / 細胞間送達 / 質量分析イメージング / 腸内細菌叢 / 母児連関 / 臓器機能 / 非感染性疾患

Outline of Final Research Achievements

In this study, we aimed to understand the pathophysiology of non-communicable diseases (NCDs) from the alterations in intercellular delivery of metabolites. By utilizing novel technologies such as mass imaging analysis and metabolome, we clarified the significance of low-molecular weight metabolites for organ function. We pointed out the roles for metabolites derived from maternal microbiota in the development of obesity and diabetes of the offspring in mice. The novel understanding of organ function from the perspective of intercellular delivery of metabolites is different from existing approach of the molecular biology which analyzes molecular function in the cell. It has brought novel results with plenty of originality that are suitable for grant-in-aid for exploratory research.

Free Research Field

内分泌学、代謝学

Academic Significance and Societal Importance of the Research Achievements

これまでの医学研究では、臓器の構成要素の一つ一つに焦点を当て、分子生物学的手法に基づき、個々の分子の細胞内の役割を検討することで、臓器機能に関する知見を断片的に集積してきた。しかしながら、実際の臓器は多数の要素で構成され、それらは液性因子を介した、お互いのコミュニケーションが円滑に行われることで初めて機能を発揮し、細胞間分子送達の変調は、非感染性疾患の発症に直結する。本研究では、臓器および生体を構成する要素の有機的連携に着目し、代謝産物の送達を介した臓器内・臓器間の情報伝達により制御される、臓器・生体における多細胞間ネットワークの解析から、臓器機能ならびにその破綻病態の理解を目指す。