Regulatory mechanism of spatiotemporal coordination of gastrointestinal motility and its medical application

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19530
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Kyushu University
• Principal Investigator: Ogawa Yoshihiro 九州大学, 医学研究院, 主幹教授 (70291424)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 消化管運動 / 高解像度食道内圧検査 / 数理モデル / 光遺伝学 / 排便中枢

Outline of Final Research Achievements

The sphincters, which are crucial for the regulation of gastrointestinal movements, require precise timing to contract and relax coordinately. Currently, the underlying mechanisms are not fully understood. Our research has concentrated on two types of sphincters: the lower esophageal sphincter, which demarcates the esophagus and stomach, which are important for the ingestion of food, and the anal sphincter, which plays a role in the excretion of waste.
Regarding the lower esophageal sphincter, we have uncovered the critical roles of mechanoreceptor channels in sensory perception and of myosin proteins in muscle fiber composition. We have also successfully replicated esophageal movements through a mathematical model that emulates and visualizes the motions. On the other hand, in the anal sphincter, we have deciphered the involvement of the brain’s defecation center in the act of defecation, shedding light on this intricate process.

Free Research Field

内科学、内分泌代謝・糖尿病学、消化器病学

Academic Significance and Societal Importance of the Research Achievements

消化管括約筋の機能障害は、消化管内容物の生理的輸送を妨げることにより、様々な疾患の発症と関連する。例えば、下部食道括約筋の機能障害は、胃内容物を食道に逆流することにより胃食道逆流症やBarrett腺癌を発症する可能性がある。一方、肛門括約筋の機能障害は、便排出障害型の慢性便秘症を発症させる。本研究成果は、消化管括約筋の機能障害により発症する良性疾患から悪性疾患の発症予測や新しい治療法の開発まで幅広い波及効果が期待される。