Erythropoietin Gene Regulation: From the Laboratory to the Bedside

Gertz, MA; Gaut, CC; Schapira, Lidia; Antin, JH; Bj, Ransil; Kh, Antman; Jp, Eder; McGarigle, CJ; Bunn, H. Franklin

doi:10.1159/000419514

Cited by 8 publications

(4 citation statements)

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“…EPO is a specific hematopoietic growth factor that functions to regulate erythropoiesis in the bone marrow [11]. The regulation of EPO gene expression occurs primarily at the mRNA level and is under the control of both transcriptional and post-transcriptional factors [12,13]. Our current results were in line with the notion that jujube exerted beneficial effect on "Qi" and "blood" deficiency animal models [1].…”

Section: Discussionsupporting

confidence: 85%

The Extract of Ziziphus jujuba Fruit (Jujube) Induces Expression of Erythropoietin Via Hypoxia-Inducible Factor-1α in Cultured Hep3B Cells

et al. 2014

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The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as health supplement or herbal medicine worldwide. To study the beneficial role of jujube in enhancing hematopoietic function, we investigated its roles on the expression of erythropoietin in cultured Hep3B human hepatocellular carcinoma cells. Application of chemically standardized jujube water extract stimulated erythropoietin expression in a dose-dependent manner, with the highest response by ~ 100 % of increase. A plasmid containing hypoxia response element, a critical regulator for erythropoietin transcription, was transfected into Hep3B cells. Application of jujube water extract onto the transfected cells induced the transcriptional activity of the hypoxia response element. To account for its transcriptional activation, the expression of hypoxia-inducible factor-1α was increased after treatment with jujube water extract: the increase was in both mRNA and protein levels. These results confirmed the hematopoietic function of jujube in the regulation of erythropoietin expression in liver cells.

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Section: Discussionsupporting

confidence: 85%

The Extract of Ziziphus jujuba Fruit (Jujube) Induces Expression of Erythropoietin Via Hypoxia-Inducible Factor-1α in Cultured Hep3B Cells

et al. 2014

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“…Growth of the human hepatoma cell line HEP3B under hypoxic conditions leads to a 50-fold increase in steady state levels of erythropoietin mRNA [20]. Transcriptional activation of the erythropoietin gene has been a primary focus for understanding hypoxic regulation of erythropoietin gene expression, although an ill-defined role for mRNA stability has been suggested [21]. Therefore, to characterize of the cellular mechanisms regulating hypoxic induction of VEGF, tRPE cells grown for various time periods in normoxic or hypoxic conditions were used for nuclear run-on analysis.…”

Section: Effect Of Hypoxia On the Transcriptional Rate Of The Vegf Genementioning

confidence: 99%

Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability

1995

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Vessel growth is often associated with ischemia. VEGF, a potent angiogenic factor, has been shown to be induced by low oxygen concentrations. These studies were conducted to investigate the molecular basis of the hypoxia-induced increase in VEGF mRNA. Run-on analysis of VEGF revealed a minimal increase in the rate of gene transcription in a human retinal epithelial cell line grown under hypoxic conditions. Examination of VEGF mRNA stability revealed that the half-life of VEGF transcripts under normoxia was short, 30-45 min, but was dramatically increased to 6-8 h in cells grown under hypoxia. Cobalt chloride, which elevates VEGF and has been suggested to be similar to hypoxia in its mechanism of action, had only a slight effect on decay rate. We postulate that hypoxia-induced increases in mRNA stability provide the sustained increases in VEGF mRNA levels necessary to support a neovascular response.

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“…In this process, EPO, a RBC-specific hormone, is able to regulate erythropoiesis in bone marrow (Ascensao et al, 1991). EPO gene expression regulates primarily at the level of transcription, and which is further controlled by a number of transcriptional and posttranscriptional factors (Schuster et al, 1989;Goldberg et al, 1991). Failure to up regulate the circulating EPO under hypoxia thereafter leads to anemia (Jelkmann, 1992).…”

Section: Jujube On Erythropoiesismentioning

confidence: 99%

A Review of Edible Jujube, the Ziziphus jujuba Fruit: A Heath Food Supplement for Anemia Prevalence

Chen

Tsim

2020

Front. Pharmacol.

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The fruits of Ziziphus jujuba, commonly known as jujube, red date or Chinese date, are taken as fresh or dried food, and as traditional medicine worldwide due to high nutritional and health values. Traditionally in China, jujube is considered as a medicinal fruit that is being used in treating blood deficiency. In this review, the beneficial effects of jujubes on the hematopoietic functions are summarized and discussed. As illustrated in cell and animal models, the application of jujube extract possessed beneficial effects, including regulation of erythropoiesis via activation of hypoxia inducible factor-induced erythropoietin, potential capacity in recycling heme iron during erythrophagocytosis and bi-directional regulation of immune response. Thus, the blood-nourishing function of jujube is being proposed here. Flavonoid, polysaccharide and triterpenoid within jujube could serve as the potential active ingredients accounting for the aforementioned health benefits. Taken together, these findings provide several lines of evidence for further development of jujube as supplementary products for prevention and/or treatment of anemia.

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Erythropoietin Gene Regulation: From the Laboratory to the Bedside

Cited by 8 publications

References 0 publications

The Extract of Ziziphus jujuba Fruit (Jujube) Induces Expression of Erythropoietin Via Hypoxia-Inducible Factor-1α in Cultured Hep3B Cells

The Extract of Ziziphus jujuba Fruit (Jujube) Induces Expression of Erythropoietin Via Hypoxia-Inducible Factor-1α in Cultured Hep3B Cells

Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability

A Review of Edible Jujube, the Ziziphus jujuba Fruit: A Heath Food Supplement for Anemia Prevalence

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