EGR4 Dotaz Zobrazit nápovědu
Fibrotic diseases are a group of pathologies with high incidence and mortality. Despite extensive research efforts, effective 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-β 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. Here we show that sustained expression of some components of MAPK signaling pathway (PDGFB, Ha-Ras(G12V) or the transcription factor EGR4) in primary chicken embryo dermal myofibroblasts results in a loss of autocrine TGF-β signaling and suppression of the myofibroblastic phenotype, characterized by the loss of alpha smooth muscle actin fibers and a substantial reduction in the production of extracellular matrix. Detailed analysis of the possible molecular mechanisms employed by EGR4 revealed FOXG1, BAMBI, NAB1, NAB2 and DUSP5 genes forming an EGR4 regulated network counteracting autocrine TGF-β signaling. We have also found that a combination of chemical inhibition of TGF-β signaling and perturbation of MAPK signaling with phorbol ester mimics the anti-fibrotic effects of PDGFB, Ha-Ras(G12V) and EGR4.
- Klíčová slova
- EGR4, FOXG1, Ha-Ras(G12V), Microarrays, Myofibroblast, PDGFB, TGF-β,
- MeSH
- aktiny genetika metabolismus MeSH
- dediferenciace buněk * MeSH
- forbolové estery farmakologie MeSH
- kuřecí embryo MeSH
- mitogenem aktivované proteinkinasy metabolismus MeSH
- myofibroblasty cytologie metabolismus MeSH
- signální transdukce MeSH
- transformující růstový faktor beta metabolismus MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aktiny MeSH
- forbolové estery MeSH
- mitogenem aktivované proteinkinasy MeSH
- transformující růstový faktor beta MeSH
