Epigenetic regulation of macrophage function in inflammatory bowel disease

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460960
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kitasato University
• Principal Investigator: Kobayashi Taku 北里大学, 北里研究所病院, 特任准教授 (10424144)
• Co-Investigator(Kenkyū-buntansha): NAKANO Masaru 北里大学, 北里研究所病院, 部長(医師) (50265807)
• Co-Investigator(Renkei-kenkyūsha): ASAI Tomohiro 静岡県立大学, 薬学部, 准教授 (00381731)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 炎症性腸疾患 / エピゲノム / マクロファージ

Outline of Final Research Achievements

We hypothesized that profiling accessible chromatin where transcription factors bind in intestinal cells from affected and non-affected individuals would identify genetically driven regulatory elements that are relevant to IBD pathology. 74 IBD associated SNPs were found in regions of open chromatin. There was statistically significant enrichment of IBD associated SNPs in regions of open chromatin in CD tissue compared to a set of random selected DNA variants with similar architecture.
Drug development based on the epigenetic modification was also attempted. Histone deacethylase inhibitors were tested for cytokine inhibition in bone-marrow derived macrophages. Belinostat showed a tendency to ameliorate acute and chronic DSS-induced colitis models.

Free Research Field

消化器内科