1996 Fiscal Year Final Research Report Summary
Pleiotrophic functions of erythropoietin and regulation of its biosynthesis.
| Project/Area Number |
05403030
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
食品科学・栄養科学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SASAKI Ryuzo Faculty of Agriculture, Kyoto University, Professor, 農学部, 教授 (60077378)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAO Masaya Faculty of Agriculture, Kyoto University, Assistant, 農学部, 助手 (10237498)
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| Project Period (FY) |
1993 – 1996
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| Keywords | Erythropoietin / Erythropoietin receptor / Astrocyte / Neuron / Neurotrophic factor / Uterus / Estradiol / Uterine capillary |
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| Research Abstract |
Erythropoietin (EPO), a glycoprotein produced by kidney in the adults, acts on erythroid precursor cells, stimulating their proliferation and differentiation. Stimulation of erythropoiesis was believed to be a sole function of EPO but we have found novel functions of EPO in the central nervous system (CNS) and female reproductive organ as followings.
(1) EPO receptor is expressed in hippocampus and cerebral cortex.
(2) EPO is produced by astrocytes in CNS and its synthesis is stimulated not only by hypoxia but also by insulin and insulin-like growth factors. The stimulation by the growth factors is due to an increased mRNA.
(3) EPO represses Glu-induced cell death of cultured neurons. Since this toxicity is the major cause of ischemia-induced neuronal death, it appears that EPO acts on neurons as a neurotrophic factor. Injection of EPO into gerbil brain suppressed with high efficiency ischemia-induced neuronal death in hippocampus and also ischemia-induced reduction in memory-learning ability.
(4) Angiogenesis is the extension of preexsisting blood vessels and is relatively inactive in the adults except for female reproductive organ. Uterine endometrium repeats its remodeling in estrous cycle of animals and menstruation cycle of primates, which accompanies angiogenesis. We have found evidence showing that EPO is involved in uterine angiogenesis.
(5) The endometrial remodeling is under control of female sexual hormone, particularly estradiol that is produced in ovary. When estradiol was given to ovariectomized mouse, rapid induction of EPO mRNA expression occurred. Furthermore, in vitro cultured uterine tissue from ovariectomized mouse produced EPO into culture media in an estradiol-dependent manner.
(6) Immunohistochemical staining showed that EPO receptor is expressed in endothelial cells of uterine capillary. These results indicate that EPO plays an important role in uterine angiogenesis.
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