Conditional deletion of IB in hematopoietic cells promotes functional recovery after spinal cord injury in mice

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16663
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Jichi Medical University
• Principal Investigator: Shiraishi Yasuyuki 自治医科大学, 医学部, 助教 (50646338)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: IκB-ζ / 脊髄損傷

Outline of Final Research Achievements

We investigated the role of IκBζ expressed in hematopoietic cells on the progression of secondary damage and functional recovery after SCI. We used conditional IκBζ-knockout mice (Mx1-Cre;Nfkbizfl/f) to examine the role of IκBζ in hematopoietic cells after SCI. Recovery of open-field locomotor performance was evaluated until 42 days post-injury. Expression patterns of inflammatory cytokines and chemokines were examined by quantitative real-time PCR or proteome array analysis. Bone marrow transplantation was also performed. Mx1-Cre;Nfkbizfl/fl mice showed significantly improved locomotor function compared with wild-type (WT) mice. Compared with WT mice, Mx1-Cre;Nfkbizfl/fl mice had significantly increased mRNA expression of interleukin (Il)-4 and Il-10 in the injured spinal cord. Transplantation of bone marrow cells from Mx1-Cre;Nfkbizfl/fl mice into WT mice improved functional recovery after SCI compared with control mice.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

IκB-ζと脊髄損傷についての報告はなく、本研究は新規性の高い研究であったと考える。本研究では、血液細胞におけるIκBζの欠損は、炎症反応のバランスを抗炎症方向、組織再生方向にシフトさせることで、脊髄損傷後の運動機能回復を促進することが示唆された。生体内でのIκBζの働きは未だ十分に解明されていないが。今後IκBζに対する研究がさらに進むことにより、細胞内のmRNA発現を抑制するsiRNAのような核酸医薬品をはじめとした、血液中のIκBζをターゲットとした脊髄損傷に対する新たな治療法が開発されることが期待される。