RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22712
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: Maruyama Kenta 生理学研究所, 生体機能調節研究領域, 特別協力研究員 (60724119)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 腸蠕動 / 大腸炎 / 骨粗鬆症 / Piezo1 / リボ核酸

Outline of Final Research Achievements

In this study, we discovered that the cation channel Piezo1 in the gut acts as a sensor of single-stranded RNA (ssRNA) governing 5-HT production. Intestinal epithelium-specific deletion of mouse Piezo1 profoundly disturbed gut peristalsis, impeded experimental colitis, and suppressed serum 5-HT levels. Because of systemic 5-HT deficiency, conditional knockout of Piezo1 increased bone formation. Notably, fecal ssRNA was identified as a natural Piezo1 ligand, and ssRNA-stimulated 5-HT synthesis from the gut was evoked in a MyD88/TRIF-independent manner. Colonic infusion of RNase A suppressed gut motility and increased bone mass. These findings suggest gut ssRNA as a master determinant of systemic 5-HT levels, indicating the ssRNA-Piezo1 axis as a potential prophylactic target for treatment of bone and gut disorders.

Free Research Field

感覚免疫学

Academic Significance and Societal Importance of the Research Achievements

腸内RNAあるいは腸内Piezo1を標的とした有効な「腸管セロトニン調節医療」が開発された場合、骨粗鬆症患者のみならず、潰瘍性大腸炎と過敏性腸症候群の患者にも福音がもたらされる可能性がある。