Unraveling the regulation of Sirt1 through TGFb and the inhibitory mechanism of Inflammatory Bowel Disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07377
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kindai University
• Principal Investigator: Amano Hisayuki 近畿大学, 医学部, 助教 (20549331)
• Co-Investigator(Kenkyū-buntansha): 岡田 斉 近畿大学, 医学部, 教授 (20280620)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: IBD / Sirtuin / 線維化

Outline of Final Research Achievements

Inflammatory Bowel Disease (IBD) might be prevented by repressing fibrosis in gut. Here, I show that the administration of nicotinamide mononucleotide (NMN), which is a metabolic intermediate on NAD+ synthetic pathway, could attenuate fibrosis in colon of mice and fibroblast activation in mouse embryonic fibroblasts (MEFs). RNA sequencing analyses in gut of wild type mice showed that inflammatory pathways were down-regulated by NMN administration. And the extracellular flux analyses showed that the oxygen consumption rate could be significantly improved by NMN in wild type MEFs, but not in Sirt1 deficient cells. Taken together, these results suggest that NMN could attenuate fibrosis in colon tissue and increase mitochondrial activity through Sirt1 and NAD+.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

今回申請者らは、炎症性腸疾患における“線維化”におけるSirt1-NAD+経路の機能に着目し、本分子経路がミトコンドリアの機能を介して線維化形成を抑制することを示した。