Table 1.
EMT-cardiac cushion associated proteins.
| ECM Proteins | Banded fold change | p-value | Functions | |
|---|---|---|---|---|
| ECM proteins | Mucin 6 | −4.2x | 0.01 | Glycoprotein indicative of glycosaminoglycans in the heart (Coram et al., 2015), where mucins are secreted by endothelial cells and play a role in cell differentiation. Mucin 6 specifically inhibits cell adhesion to the extracellular matrix and hinders cell invasion (Leir and Harris, 2011). |
| Fibulin-1 | −1.3x | <0.01 | Glycoprotein that suppresses EMT in the proximal outflow tract during valve morphogenesis, by repressing TGFβ2 and Snail1 levels (Harikrishnan et al., 2015). | |
| Laminin α 4 (LAMA4) | −1.2x | 0.02 | Cushion basal lamina component that stabilizes the endothelium and acts as a barrier to migratory cells (Medici and Kalluri, 2012), and becomes intermittently distributed after EMT onset (Nakajima et al., 1997). | |
| Laminin γ1 (LAMC1) | −1.1x | 0.07 | ||
| Syndecan 2 (SDC2) | +1.3x | 0.01 | Heparin sulfate proteoglycan which can concentrate glycoproteins, collagens, and growth factors ligands found in the extracellular matrix (Lockhart et al., 2011). | |
| Plasminogen activator 1 (PAI-1) | +1.1x | 0.10 | Enzyme that degrades basal lamina so that endocardial cells can invade the cardiac jelly, before other migration-inducing proteins fill the cushions (McGuire and Alexander, 1993). | |
| Tenascin C (TNC) | −1.3x* | 0.01 | Glycoprotein associated with cushion EMT that stimulates the TGFβ pathway (Imanaka-Yoshida and Aoki, 2014). | |
| Collagen 1, α2 (COL1a2) | −1.2x* | 0.08 | Type I collagen that has been associated with EMT activation (Medici and Kalluri, 2012). | |
| Cell type markers | VE-Cadherin (VE-Cad) | +1.1x* | 0.10 | Endocardial junction marker (Person et al., 2005). |
| Angiopoietin 2 (ANG-2) | −1.2x | 0.04 | Endothelial marker; member of the VEGF family and largely specific for vascular endothelium (Vijayaraj et al., 2012). | |
| Vitronectin | +1.4x | <0.01 | Mesenchymal marker that is activated by Snail (Xu et al., 2009). | |
| Myosin-11 (MYH-11) | +1.5x | 0.04 | Late myogenic differentiation marker. Myosin-11 is a smooth muscle myosin belonging to the myosin heavy chain family. A portion of mesenchymal transitioned cells further differentiate into smooth muscle cells (Lin et al., 2012). | |
| Calponin 3 (CNN3) | −1.2x* | 0.04 | Mesenchymal marker (Moonen et al., 2015). | |
| EMT regulators | YAP1 | +1.2x | 0.06 | Transcription factor that promotes TGFβ-induced upregulation of Snail, Twist1, and Slug during cardiac cushion development (Zhang et al., 2014). |
| Vascular endothelial growth factor receptor (VEGFr) | −1.3x | 0.03 | Receptor for VEGF ligand whose expression suppresses EMT during early valvulogenesis (Wang et al., 2016). | |
| α actinin 4 (ACTN4) | +1.2x | 0.04 | Microfilament protein associated with assembly and maintenance of the actin cytoskeleton in developing valves (Barnette et al., 2014), that promotes EMT through Snail signaling in cervical cancer (An et al., 2016). | |
| Integrin α5 (ITGA5) | −1.2x | 0.03 | Integrins that mediate cell-matrix adhesion, where a change in the level of expression (an integrin switch) often reflects alterations in cell-matrix interactions (Zeisberg and Neilson, 2009). | |
| Integrin β3 (ITGB3) | −1.2x | 0.06 | ||
*
Protein abundance change is not as expected based on increased EMT.