Hepatic Erythropoietin Gene Regulation by GATA-4

Dame, Christof; Sola, Martha C.; Lim, Kim Chew; Leach, Kelly M.; Fandrey, Joachim; Ma, Yaluan; Knöpfle, G; Engel, James Douglas; Bungert, Jörg

doi:10.1074/jbc.m310404200

Cited by 88 publications

(88 citation statements)

References 64 publications

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“…1). The murine Gata4 siRNA sequence is almost identical to a human GATA4 siRNA sequence, which effectively reduced GATA4 in human hepatoma cells (Dame et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The Gata4 siRNA sequence (TCTCGATATGTTTGATGAC) is almost identical to a human GATA4 siRNA (NCBI accession no. L34357; nt 852-870 relative to the transcription start site: TCTCGATATGTTTGACGAC) that has previously been shown to efficiently reduce GATA4 expression in human hepatoma Hep3B cells (Dame et al 2004). Normal expression levels of Gata2 mRNA demonstrated that Gata4 siRNA is specific.…”

Section: In Vitro Efficacy Of Gata4 Rnaimentioning

confidence: 99%

“…Transfer was performed using the Mini Protean apparatus (Bio-Rad). Incubation with antibodies (anti-GATA2 (H116), anti-GATA4 (C-20), anti-GATA4 (H-112), anti-a-Tubulin (TU-02), or anti-b-Actin (AC-15); all from Santa Cruz Biotechnology, Santa Cruz, CA, USA) and later detection of signals with appropriate HRP conjugated secondary antibodies were performed as previously described (Dame et al 2004). …”

Section: Western Blot Analysismentioning

confidence: 99%

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Transgenic mice expressing small interfering RNA against Gata4 point to a crucial role of Gata4 in the heart and gonads

Thurisch

Liang²,

Sarioglu³

et al. 2009

Journal of Molecular Endocrinology

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Homozygous deficiency of the transcription factor Gata4 in mice causes lethality due to defects in ventral morphogenesis and heart tube formation. There is increasing evidence demonstrating that GATA4 function is also relevant for normal developed organ systems, including the heart and endocrinum. To analyze the implication of Gata4 beyond development, we generated transgenic mice expressing inducible small interfering RNA against Gata4. In longitudinal analysis, efficient suppression of Gata4 mRNA (down to 80% of wild-type levels) and protein expression in the heart was detected 38 days after induction of Gata4 short hairpin RNA. Decreased Gata4 expression was associated with reduction in the expression of known cardiac target genes, but the function of the heart remained unperturbed at 20-30% of normal Gata4 levels. Interestingly, Gata4 expression was almost abolished in the ovary and testis. This was accompanied in the testis by a significant reduction of GATA4 downstream target genes, such as the genes encoding Mullerian inhibiting substance (MIS) and steroidogenic acute regulatory (StAR) protein. By contrast, expression levels of Mis and Star were only slightly modified in the ovary, and concentrations of circulating FSH and LH were normal in female transgenic mice after induction of Gata4 short hairpin RNA. However, inhibition of Gata4 expression led to the formation of ovarian teratoma in 10% of females. Histology of the teratomas showed predominantly ectodermal and mesodermal structures. Our data demonstrate that Gata4 is critically involved in the function and integrity of the gonads in vivo.

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“…1). The murine Gata4 siRNA sequence is almost identical to a human GATA4 siRNA sequence, which effectively reduced GATA4 in human hepatoma cells (Dame et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Section: In Vitro Efficacy Of Gata4 Rnaimentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

See 1 more Smart Citation

Transgenic mice expressing small interfering RNA against Gata4 point to a crucial role of Gata4 in the heart and gonads

Thurisch

Liang²,

Sarioglu³

et al. 2009

Journal of Molecular Endocrinology

Self Cite

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“…GATA-4 is expressed exclusively in hepatocytes and binds strongly to this GATA motif, enhancing Epo expression (Dame et al 2004). The marked reduction in expression of hepatic GATA-4 following birth is likely an important contributor to the switch in Epo production from liver to kidney (Dame et al 2004).…”

Section: Regulation Of the Epo Genementioning

confidence: 99%

Erythropoietin

Bunn

2013

Cold Spring Harbor Perspectives in Medicine

210

171

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During the past century, few proteins have matched erythropoietin (Epo) in capturing the imagination of physiologists, molecular biologists, and, more recently, physicians and patients. Its appeal rests on its commanding role as the premier erythroid cytokine, the elegant mechanism underlying the regulation of its gene, and its remarkable impact as a therapeutic agent, arguably the most successful drug spawned by the revolution in recombinant DNA technology. This concise review will begin with a synopsis of the colorful history of this protein, culminating in its purification and molecular cloning. It then covers in more detail the contemporary understanding of Epo's physiology as well as its structure and interaction with its receptor. A major part of this article focuses on the regulation of the Epo gene and the discovery of HIF, a transcription factor that plays a cardinal role in molecular adaptation to hypoxia. In the concluding section, a synopsis of Epo's role in disorders of red blood cell production will be followed by an assessment of the remarkable impact of Epo therapy in the treatment of anemias, as well as concerns that provide a strong impetus for the development of even safer and more effective treatment.

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“…Dame et al (59) reported that GATA-4 is critically involved in EPO gene expression and may be responsible for the switch in the site of EPO production from the fetal liver to the adult kidney. In addition, GATA-2 inhibits EPO gene transcription by binding to the GATA sequence on the EPO promoter, thereby leading to downregulation of EPO mRNA expression and subsequent EPO synthesis (60).…”

Section: Gata Inhibitionmentioning

confidence: 99%

Novel Erythropoiesis-Stimulating Agents

Macdougall

2008

Clinical Journal of the American Society of Nephrology

102

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Nearly two decades ago, recombinant human erythropoietin transformed the management of chronic kidney disease anemia by allowing a more sustained increase in hemoglobin than was possible by intermittent blood transfusion. The treatment was highly effective, but because of the fairly short half-life of the molecule at approximately 6 to 8 h, injections usually had to be administered two to three times weekly. A second-generation erythropoietin analogue, darbepoetin alfa, was then created, with a longer elimination half-life in vivo that translated into less frequent dosing, usually once weekly or once every 2 wk. More recently, another erythropoietin-related molecule has been produced called Continuous Erythropoietin Receptor Activator with an even greater half-life, and other molecules are in development or are being licensed, including biosimilar epoetin products and Hematide. The latter is a synthetic peptide-based erythropoietin receptor agonist that, interestingly, has no structural homology with erythropoietin, and yet is still able to activate the erythropoietin receptor and stimulate erythropoiesis. The search goes on for orally active antianemic therapies, and several strategies are being investigated, although none is imminently available. This article reviews the latest progress with these novel erythropoietic agents in this new era in anemia management.

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Hepatic Erythropoietin Gene Regulation by GATA-4

Cited by 88 publications

References 64 publications

Transgenic mice expressing small interfering RNA against Gata4 point to a crucial role of Gata4 in the heart and gonads

Transgenic mice expressing small interfering RNA against Gata4 point to a crucial role of Gata4 in the heart and gonads

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Novel Erythropoiesis-Stimulating Agents

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