2018 Fiscal Year Final Research Report
Systemic mechanisms of response to hypoxic stresses
| Project Area | Oxygen biology: a new criterion for integrated understanding of life |
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| Project/Area Number |
26111002
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 教郎 東北大学, 医学系研究科, 准教授 (20447254)
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| Research Collaborator |
SEKINE Hiroki 東北大学, 加齢医学研究所, 助教
HIRANO Ikuo 東北大学, 大学院医学系研究科 分子血液分野, 助教
NEZU Masahiro 東北大学, 大学院医学系研究科, 大学院生
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| Project Period (FY) |
2014-07-10 – 2019-03-31
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| Keywords | 低酸素応答 / 酸化ストレス応答 / 遺伝子改変マウス / 転写制御 / 赤血球 / 炎症 |
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| Outline of Final Research Achievements |
A lack of oxygen causes harmful hypoxic stress in cells and organs, while oxygen is also a source of harmful oxidative stressors, including reactive oxygen species. Because oxygen is delivered into every organ by erythrocytes, cellular oxygen levels largely depend on the circulation of erythrocytes. Erythrocyte production is mainly controlled by the erythroid growth factor erythropoietin (Epo) which is secreted by REP (renal Epo producing) cells in a hypoxia-inducible manner. This study elucidated the regulatory mechanism of Epo production in REP cells, and demonstrated that defects in the mechanism are closely associated with the pathogenesis and progression of many types of diseases through the synergistic effects of hypoxic and oxidative stresses. These results confirm that therapeutic strategies targeting the cellular mechanisms of adaptation to hypoxic or oxidative stress, which are currently going on clinical trials, are plausible for treating a variety of diseases.
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| Free Research Field |
医化学
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| Academic Significance and Societal Importance of the Research Achievements |
腎臓病、糖尿病、貧血、妊娠高血圧などの病態モデルを用いて、酸素に関係する生体応答機構の果たす重要な役割について明らかにしたことにより、様々な疾患の分子病態が理解され、創薬標的同定や革新的治療法確立につながる成果を得ることができた。実際に、研究成果に関する国内外での報道や科学番組での紹介により、大きな反響を得ている。また、国内で臨床試験の進められている腎性貧血治療薬の作用を裏付ける分子基盤を提供した。さらに、酸化ストレス応答系に関する一連の研究成果は、腎臓病の創薬標的となり、国内で第III相臨床試験が行われるまでに結実した。
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