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Experimental & Molecular Medicine ; : 674-683, 2012.
Article in English | WPRIM | ID: wpr-149761

ABSTRACT

Relative deficiency in production of glycoprotein hormone erythropoietin (Epo) is a major cause of renal anemia. This study planned to investigate whether the hypoxia-regulated system of Epo expression, constructed by fusing Epo gene to the chimeric phosphoglycerate kinase (PGK) hypoxia response elements (HRE) in combination with cytomegalovirus immediate-early (CMV IE) basal gene promoter and delivered by plasmid intramuscular injection, might provide a long-term physiologically regulated Epo secretion expression to correct the anemia in adenine-induced uremic rats. Plasmid vectors (pHRE-Epo) were synthesized by fusing human Epo cDNA to the HRE/CMV promoter. Hypoxia-inducible activity of this promoter was evaluated first in vitro and then in vivo in healthy and uremic rats (n = 30 per group). The vectors (pCMV-Epo) in which Epo expression was directed by a constitutive CMV gene promoter served as control. ANOVA and Student's t-test were used to analyze between-group differences. A high-level expression of Epo was induced by hypoxia in vitro and in vivo. Though both pHRE-Epo and pCMV-Epo corrected anemia, the hematocrit of the pCMV-Epo-treated rats exceeded the normal (P < 0.05), but that of the pHRE-Epo-treated rats didn't. Hypoxia-regulated system of Epo gene expression constructed by fusing Epo to the HRE/CMV promoter and delivered by plasmid intramuscular injection may provide a long-term and stable Epo expression and secretion in vivo to correct the anemia in adenine-induced uremic rats.


Subject(s)
Animals , Humans , Rats , Anemia/blood , Base Sequence , Blood Urea Nitrogen , Cell Hypoxia , Creatinine/blood , Erythropoietin/biosynthesis , Gene Expression Regulation , Genes, Reporter , Genetic Therapy , HeLa Cells , Injections, Intramuscular , Kidney/pathology , Luciferases, Firefly/biosynthesis , Molecular Sequence Data , Plasmids/genetics , Promoter Regions, Genetic , Rats, Sprague-Dawley , Recombinant Proteins/biosynthesis , Response Elements , Transcriptional Activation , Uremia/blood
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