Mechanism of adaptation to chronic hypoxia
| Project/Area Number |
25670157
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
Suzuki Norio 東北大学, 医学(系)研究科(研究院), 講師 (20447254)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | 低酸素応答 / 転写制御 / 貧血 / 代謝制御 / 遺伝子改変マウス / エリスロポエチン / 代謝 |
|---|
| Outline of Final Research Achievements |
To elucidate the mechanism of adaptation to chronic hypoxia, we analyzed a genetically modified mouse line, in which the erythroid growth factor erythropoietin (Epo) expression was restricted in the liver. Because of loss of Epo-gene expression in the kidney, the major Epo-producing organ in adult animals, the mice developed severe anemia. Although the anemic mice exhibited systemic and chronic hypoxia, their lifespan was normal. Gene expression profiles in livers of the anemic mice were compared with those of a transgenic mouse line over-expressing HIFs (hypoxia-inducible transcription factors) the major regulator for cellular hypoxia responses. The hypoxia-inducible genes were upregulated in both lines, indicating that the HIF pathway plays a central role in adaptation to both acute and chronic hypoxia. The anemic mice showed the extremely higher induction level of gene X than the HIF transgenic mice, suggesting that the gene X product is involved in adaptation to chronic hypoxia.
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Report
(4 results)
Research Products
(48 results)
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[Journal Article] Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia Signaling2016
Author(s)
Tomokazu Souma, Masahiro Nezu, Daisuke Nakano, Shun Yamazaki, Ikuo Hirano, Hiroki Sekine, Takashi Dan, Kotaro Takeda, Guo-Hua Fong, Akira Nishiyama, Sadayoshi Ito, Toshio Miyata, Masayuki Yamamoto, Norio Suzuki
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Journal Title
Journal of the american society of nephlorogy
Volume: 27
Issue: 2
Pages: 428-438
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Hypoxia Signaling Cascade for Erythropoietin Production in Hepatocytes.2015
Author(s)
Tojo Y, Sekine H, Hirano I, Pan X, Souma T, Tsujita T, Kawaguchi S, Takeda N, Takeda K, Fong GH, Dan T, Ichinose M, Miyata T, Yamamoto M, Suzuki N.
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Journal Title
Mol Cell Biol.
Volume: 35
Issue: 15
Pages: 2658-2672
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Plasticity of renal erythropoietin-producing cells governs fibrosis2013
Author(s)
Souma T, Yamazaki S, Moriguchi T, Suzuki N, Hirano I, Pan X, Minegishi N, Abe M, Kiyomoto H, Ito S, Yamamoto M
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Journal Title
J Am Soc Nephrol
Volume: 24
Issue: 10
Pages: 1599-1616
DOI
Related Report
Peer Reviewed / Open Access
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