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    Title: Granulocyte Colony-Stimulating Factor Activating HIF-1a Acts Synergistically with Erythropoietin to PromoteTissue Plasticity
    Authors: Shih-Ping Liu;Shin-Da Lee;Hsu-Tung Lee;Demeral David Liu;Hsiao-Jung Wang;Ren-Shyan Liu;Shinn-Zong Lin;Woei-Cherng Shyu
    Contributors: 健康產業管理學系
    Date: 2010-04
    Issue Date: 2012-11-26 12:06:34 (UTC+8)
    Abstract: "Stroke and peripheral limb ischemia are serious clinical problems with poor prognosis and limited treatment. The
    cytokines erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) have been used to induce endogenous
    cell repair and angiogenesis. Here, we demonstrated that the combination therapy of EPO and G-CSF exerted synergistic
    effects on cell survival and functional recovery from cerebral and peripheral limbs ischemia. We observed that even under
    normoxic conditions, G-CSF activates hypoxia-inducible factor-1a (HIF-1a), which then binds to the EPO promoter and
    enhances EPO expression. Serum EPO level was significantly increased by G-CSF injection, with the exception of Tg-HIF-
    mice. The neuroplastic mechanisms exerted by EPO combined with G-CSF included enhanced expression of the
    antiapoptotic protein of Bcl-2, augmented neurotrophic factors synthesis, and promoted neovascularization. Further, the
    combination therapy significantly increased homing and differentiation of bone marrow stem cells (BMSCs) and intrinsic
    neural progenitor cells (INPCs) into the ischemic area. In summary, EPO in combination with G-CSF synergistically
    enhanced angiogenesis and tissue plasticity in ischemic animal models, leading to greater functional recovery than either
    agent alone."
    Relation: PUBLIC LIBRARY of SCIENCE,5(4):e10093.
    Appears in Collections:[Department of Healthcare Administration] Journal Article

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