The role of Nr4a3 on intestinal homeostasis

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19367
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: Keita Saeki 慶應義塾大学, 医学部(信濃町), 特任助教 (80528729)
• Research Collaborator: YOSHIMURA Akihiko 慶應義塾大学, 医学部, 教授 (90182815)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: カルシトニン関連ペプチド / セロトニン / 大腸炎 / ヒルシュスプルング病 / 核内オーファン受容体 / 腸管神経叢

Outline of Final Research Achievements

We focused on Nr4a3 orphan receptor and how it regulates intestinal homeostasis. Human Nr4a3 gene is located on chromosome 9q31.1 region where the unidentified causative gene of Hirschsprung disease is. In absence of Nr4a3 in mice, the colon has hypoplastic ganglia in its myenteron and wriggles more slowly than wild type. Furthermore, Nr4a3-deficient mice are resistant to dextran sodium sulfate induced acute colitis. This resistance is partially cancelled by giving 5-HT1A agonist and calcitonin gene related peptide seems to be a key regulator for this. Our findings demonstrate novel mechanism of neuro-gut axis in gut motility and inflammation and make a breakthrough in the diagnosis of HSCR subtypes and therapy for novel intestinal inflammatory diseases.

Free Research Field

医歯 薬学 内科系臨床医学　消化器内科学　　8202