Metabolic adaptation of inflammatory diseases

2021 Fiscal Year Final Research Report

• Project Area: Transomic Analysis of Metabolic Adaptation
• Project/Area Number: 17H06302
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: OKADA MARIKO 大阪大学, 蛋白質研究所, 教授 (10342833)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: シグナル伝達 / 炎症 / 免疫応答 / NF-kB / オミクス

Outline of Final Research Achievements

NF-kB transcription factor controls induction of various genes in inflammation and immune response, however, their molecular basis largely remains unclear. In this study, we clarified the functional mechanism of NF-kB by quantitatively analyzing various omics data obtained from next-generation sequences using immune B cells, breast cancer cells, and atopic dermatitis animal models. As a result, it was shown that the chromatin opening in the enhancer and promoter regions and the number of DNA bindings of the NF-kB molecule are important for enhancing the expression of the target gene by NF-kB. It was also shown that NF-kB induces liquid-liquid phase separation (LLPS) -like molecular interactions in the nucleus and increases cellular heterogeneity in gene expression.

Free Research Field

システム生物学

Academic Significance and Societal Importance of the Research Achievements

炎症疾患や免疫応答において、NF-kB転写因子は重要な働きを示す。このような疾患において、特に問題となるのは、ある時突然に症状が現れ、それがなかなかもとに戻らない状態になることである。このような反応は、生体内の反応が閾値を超えたため、症状となって現れると考えられているが、NF-kBはこの閾値の決定機構に重要な役目を果たすことが明らかになった。特に、細胞核内に存在するNF-kB量とDNAの状態がNF-kBが結合しやすいかどうかによって、この制御が決定される。特に、アトピー性皮膚炎などにおいては、細菌の感染などを防ぎ、NF-kBの核内量を減らすことが重要になる。