Involvement of the MEKK1 signaling pathway in the regulation of epicardial cell behavior by hyaluronan
| Autor: | Anita F. Austin, Todd D. Camenisch, Patti Parker, Joey V. Barnett, Evisabel A. Craig |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
MAP Kinase Signaling System
Cellular differentiation Cell MAP Kinase Kinase Kinase 1 Mice Transgenic Cell fate determination Article Cell Line Extracellular matrix Mice Cell Movement medicine Animals Hyaluronic Acid Extracellular Signal-Regulated MAP Kinases Transcription factor biology CD44 NF-kappa B Cell Differentiation Cell Biology Transfection Cell biology Hyaluronan Receptors Serum Response Element medicine.anatomical_structure biology.protein Snail Family Transcription Factors Signal transduction Pericardium Transcription Factors |
| Zdroj: | Cellular Signalling. 22:968-976 |
| ISSN: | 0898-6568 |
| Popis: | During embryonic development, cells comprising the outermost layer of the heart or epicardium play a critical role in the formation of the coronary vasculature. Thus, uncovering the molecular mechanisms that govern epicardial cell behavior is imperative to better understand the etiology of cardiovascular diseases. In this study, we investigated the function of hyaluronan (HA), a major component of the extracellular matrix, in the modulation of epicardial signaling. We show that stimulation of epicardial cells with high molecular weight HA (HMW-HA) promotes the association of MEKK1 with the HA receptor CD44 and induces MEKK1 phosphorylation. This leads to the activation of two distinct pathways, one ERK-dependent and another NFkappaB-dependent. Furthermore, HMW-HA stimulates epicardial cells to differentiate and invade, as suggested by increased vimentin expression and enhanced invasion through a collagen matrix. Blockade of CD44, transfection with a kinase-inactive MEKK1 construct or the use of ERK1/2 and NFkappaB inhibitors significantly abrogates the invasive response to HMW-HA. Together, these findings suggest an important role for HA in the regulation of epicardial cell fate via activation of MEKK1 signaling cascades. |
| Databáze: | OpenAIRE |
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