Cooperative signaling between cytokine receptors and the glucocorticoid receptor in the expansion of erythroid progenitors: molecular analysis by expression profiling
| Autor: | Montserrat Blázquez-Domingo, Sebastian Carotta, Andrea Kolbus, Walbert Bakker, Marieke von Lindern, Hartmut Beug, Susanna Luedemann, Peter Steinlein |
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| Přispěvatelé: | Hematology, Other departments, Landsteiner Laboratory |
| Rok vydání: | 2003 |
| Předmět: |
Cellular differentiation
Immunology Stem cell factor Biology Biochemistry Dexamethasone Transactivation Mice Glucocorticoid receptor Receptors Glucocorticoid hemic and lymphatic diseases medicine Animals Receptors Cytokine Erythropoietin Oligonucleotide Array Sequence Analysis Regulation of gene expression Erythroid Precursor Cells Stem Cell Factor Gene Expression Profiling Cell Biology Hematology Receptor Cross-Talk Mice Mutant Strains Cell biology Gene expression profiling Gene Expression Regulation Cancer research Signal transduction hormones hormone substitutes and hormone antagonists medicine.drug Signal Transduction |
| Zdroj: | Blood, 102, 3136-3146. American Society of Hematology Blood, 102(9), 3136-3146. American Society of Hematology |
| ISSN: | 0006-4971 |
| Popis: | Erythroid progenitors undergo renewal (proliferation without apparent differentiation) in response to erythropoietin (Epo), stem cell factor (SCF), and glucocorticoids (dexamethasone) (Dex). SCF and Dex cooperate with Epo to promote proliferation and inhibit differentiation of erythroid progenitors, while Epo alone is required to protect erythroid cells from apoptosis during terminal red cell maturation. To examine the mechanism of the synergistic interactions of Epo, SCF, and Dex, we analyzed gene expression patterns using DNA chip–based large-scale comparative gene profiling using microarrays enriched in hematopoietic transcripts or containing randomly selected genes. Differentially regulated genes were validated by real-time reverse transcription–polymerase chain reaction (RT-PCR). The results reveal cooperative regulation of gene expression by glucocorticoids and Epo/SCF on a number of genes, such as CIS, BTG1, VDUP1, CXCR4, GILZ, and RIKEN29300106B05. While Epo and SCF never showed opposite effects on gene expression, Dex either enhanced or attenuated the effect of Epo and/or SCF. Several glucocorticoid receptor (GR)–target genes were regulated by Dex only in the presence of Epo and/or SCF, suggesting that the GR functions in the context of a larger transactivation complex to regulate these genes. The data also suggest that modulation of cytokine-induced signals by the GR is an important mechanism in erythroid progenitor renewal. |
| Databáze: | OpenAIRE |
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