Mechanism of adaptation to chronic hypoxia

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670157
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: Suzuki Norio 東北大学, 医学(系)研究科(研究院), 講師 (20447254)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 低酸素応答 / 転写制御 / 貧血 / 代謝制御

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.

Free Research Field

分子生物学