2022 Fiscal Year Final Research Report
Pathological involvement of monocyte/macrophages in wound healing and vascular abnormalities in systemic sclerosis
Project/Area Number |
20K08656
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53050:Dermatology-related
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Research Institution | Yokohama City University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 創傷治癒 / 単球マクロファージ / 全身性強皮症 |
Outline of Final Research Achievements |
This study was aimed to evaluate whether IRF8 is involved in abnormal wound healing and vasculopathy as critical features of SSc pathology. An involvement of IRF8 in wound healing process was evaluated in full-thickness skin wound model and wound closure was further assessed in myeloid-specific IRF8 knockout mice (IRF8KO). Upregulation of IRF8 was observed in skin wound model of WT, suggesting IRF8 involvement in wound healing. Wound closure was significantly delayed in IRF8KO mice. Histological analysis found smaller granulation tissue in IRF8KO mice. mRNA levels of adhesion and angiogenesis-related factors such as S1pr1, GlyCAM1, and P-Selectin were upregulated and amphiregulin was downregulated in IRF8KO mice. Abnormal angiogenesis with enhanced number of small vessels was observed in IRF8 KO mice. The results suggest that IRF8 in myeloid lineage cells plays important roles in wound healing and may mimic a part of SSc pathology.
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Free Research Field |
線維化、膠原病
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Academic Significance and Societal Importance of the Research Achievements |
全身性強皮症は、血管障害と過剰線維化の双方が主要な病態であり、両者を一元化する病態解明、新規治療開発が重要な課題である。単球マクロファージ系細胞が、強皮症の病態に重要な関与をしていることはこれまでも示唆されており、我々は、その分化制御を行う転写因子に着目した解析を行ってきた。これまでの研究と今回の研究により、線維化と創傷治癒異常・血管異常の双方にIRF8が関与する可能性が示唆されている。強皮症の血管異常におけるIRF8の関与をさらに深く解明することで、新規治療開発に結び付けられる可能性がある。
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