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Status |
Public on Mar 05, 2010 |
Title |
An Antifibrotic Regulatory Network Governed by the Transcription Factor EGR4 |
Organism |
Gallus gallus |
Experiment type |
Expression profiling by array
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Summary |
Fibrotic diseases are a group of pathologies with high incidence and mortality. Despite extensive research efforts, efficient therapies are still not available. Understanding the molecular mechanisms driving the onset, progression and possible resolution of fibrosis is a prerequisite to the development of successful therapies. The central role of the TGF-beta pathway and myofibroblasts in the pathogenesis of fibrosis is now generally accepted. The possible mechanisms of myofibroblast elimination or dedifferentiation, on the other hand, are still almost uncharted territory. Basic fibroblast growth factor (bFGF) is able to suppress myofibroblastic differentiation of mesenchymal cells, but the underlying mechanism has not been studied in detail. Here, we show that sustained expression of the transcription factor EGR4, which is inducible by bFGF, in primary chicken embryo dermal myofibroblasts results in suppression of the myofibroblastic phenotype, characterized by the loss of smooth muscle actin fibers and a substantial reduction in the production of extracellular matrix. Detailed analysis of the possible molecular mechanisms revealed FOXG1, BAMBI, NAB1, NAB2 and DUSP5 genes forming an EGR4 regulated network counteracting autocrine TGF-beta signaling.
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Overall design |
Comparison of expression profiles of chicken embryo dermal myofibroblasts infected with retroviral construct SFCVneo-EGR4 versus chicken embryo dermal myofibroblasts infected with empty retroviral vector SFCVneo. Three biological replicates were analyzed for each group.
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Contributor(s) |
Cermak V |
Citation(s) |
24315689 |
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Submission date |
Mar 06, 2009 |
Last update date |
Aug 19, 2016 |
Contact name |
Vladimir Cermak |
E-mail(s) |
cermak@img.cas.cz
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Organization name |
Institute of Molecular Genetics, Czech Academy of Sciences
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Lab |
Molecular Virology
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Street address |
Videnska 1083
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City |
Prague |
ZIP/Postal code |
14220 |
Country |
Czech Republic |
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Platforms (1) |
GPL3213 |
[Chicken] Affymetrix Chicken Genome Array |
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Samples (6)
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GSM378375 |
Primary skin fibroblasts infected with empty retroviral vector SFCVneo replicate 1 |
GSM378376 |
Primary skin fibroblasts infected with empty retroviral vector SFCVneo replicate 2 |
GSM378377 |
Primary skin fibroblasts infected with empty retroviral vector SFCVneo replicate 3 |
GSM378378 |
Primary skin fibroblasts infected with retroviral construct SFCVneo-EGR4 replicate 1 |
GSM378379 |
Primary skin fibroblasts infected with retroviral construct SFCVneo-EGR4 replicate 2 |
GSM378380 |
Primary skin fibroblasts infected with retroviral construct SFCVneo-EGR4 replicate 3 |
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Relations |
BioProject |
PRJNA114905 |