Regulation of inflammatory diseases by pyruvate kinase M2
Project/Area Number |
18K16136
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 細胞内代謝 / PKM2 / マクロファージ / 解糖系 / ピルビン酸キナーゼM2 / 膠原病 / 炎症性疾患 |
Outline of Final Research Achievements |
Pyruvate kinase M2, which is one of the enzymes involved in glycolysis, has been recognized as the enzyme expressed specifically in cancer cells. We had revealed that PKM2 was also regulating inflammatory activity in activated immune cells. In this study, we evaluated the effects of PKM2 activator to examine the functions of PKM2 in activated immune cells including macrophages and T cells. The results indicated that PKM2 regulated the activation of macrophages to M1 phenotype, and also involved in T cell differentiation. In MRL/lpr mice, PKM2 was considered to regulate lpr cells. Furthermore, PKM2 was involved in the regulation of T cell differentiation, and was possible to be associated with the altered immune responses in autoimmune diseases.
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Academic Significance and Societal Importance of the Research Achievements |
がん細胞において重要と考えられてきた酵素であるピルビン酸キナーゼM2(PKM2)が、免疫システムの活性化においても重要な役割を果たしていることが明らかになった。これにより、免疫細胞の異常活性化が原因となる膠原病を含む自己免疫疾患において、がん細胞と同様の細胞代謝を標的とする治療方法が有用である可能性が示唆されるとともに、がん細胞周囲の免疫反応においても機能している可能性が考慮される。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis.2020
Author(s)
Mutoh T, Shirai T, Ishii T, Shirota Y, Fujishima F, Takahashi F, Kakuta Y, Kanazawa Y, Masamune A, Saiki Y, Harigae H, Fujii H.
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Journal Title
Nat Commun.
Volume: 11(1)
Issue: 1
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Takayasu Arteritis Coexisting with Sclerosing Osteomyelitis2018
Author(s)
Shirai T, Hanaoka R, Goto Y, Kojima I, Ishii Y, Hoshi Y, Fujita Y, Shirota Y, Fujii H, Ishii T, Harigae H.
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Journal Title
Internal Medicine
Volume: 57
Issue: 13
Pages: 1929-1934
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2018-07-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Multicenter double-blind randomized controlled trial to evaluate the effectiveness and safety of bortezomib as a treatment for refractory systemic lupus erythematosus.2018
Author(s)
Ishii T, Tanaka Y, Kawakami A, Saito K, Ichinose K, Fujii H, Shirota Y, Shirai T, Fujita Y, Watanabe R, Chiu SW, Yamaguchi T, Harigae H.
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Journal Title
Modern Rheumatology
Volume: -
Issue: 6
Pages: 1-7
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Optimized Protocol for Extracorporeal Shock Wave Therapy on Digital Ulcers in Systemic Sclerosis2018
Author(s)
Tomonori Ishii, Yasushi Kawaguchi, Osamu Ishikawa, Hiromitsu Takemori, Naruhiko Takasawa, Hitoshi Kobayashi, Yuichi Takahashi, Hidekata Yasuoka, Takao Kodera, Osamu Takai, Izaya Nakaya, Tomomasa Izumiyama, Hiroshi Fujii, Yukiko Kamogawa, Yuko Shirota, Tsuyoshi Shirai et al.
Organizer
American College of Rheumatology
Related Report
Int'l Joint Research
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