Exp Mol Med.  2014 Sep;46(9):e115. 10.1038/emm.2014.59.

Preeclampsia serum-induced collagen I expression and intracellular calcium levels in arterial smooth muscle cells are mediated by the PLC-gamma1 pathway

• Jiang R
• Teng Y
• Huang Y
• Gu J
• Ma L
• Li M
• Zhou Y

• KMID: 2155380
• DOI: http://doi.org/10.1038/emm.2014.59

Abstract

In women with preeclampsia (PE), endothelial cell (EC) dysfunction can lead to altered secretion of paracrine factors that induce peripheral vasoconstriction and proteinuria. This study examined the hypothesis that PE sera may directly or indirectly, through human umbilical vein ECs (HUVECs), stimulate phospholipase C-gamma1-1,4,5-trisphosphate (PLC-gamma1-IP3) signaling, thereby increasing protein kinase C-alpha (PKC-alpha) activity, collagen I expression and intracellular Ca2+ concentrations ([Ca2+]i) in human umbilical artery smooth muscle cells (HUASMCs). HUASMCs and HUVECs were cocultured with normal or PE sera before PLC-gamma1 silencing. Increased PLC-gamma1 and IP3 receptor (IP3R) phosphorylation was observed in cocultured HUASMCs stimulated with PE sera (P<0.05). In addition, PE serum significantly increased HUASMC viability and reduced their apoptosis (P<0.05); these effects were abrogated with PLC-gamma1 silencing. Compared with normal sera, PE sera increased [Ca2+]i in cocultured HUASMCs (P<0.05), which was inhibited by PLC-gamma1 and IP3R silencing. Finally, PE sera-induced PKC-alpha activity and collagen I expression was inhibited by PLC-gamma1 small interfering RNA (siRNA) (P<0.05). These results suggest that vasoactive substances in the PE serum may induce deposition in the extracellular matrix through the activation of PLC-gamma1, which may in turn result in thickening and hardening of the placental vascular wall, placental blood supply shortage, fetal hypoxia-ischemia and intrauterine growth retardation or intrauterine fetal death. PE sera increased [Ca2+]i and induced PKC-alpha activation and collagen I expression in cocultured HUASMCs via the PLC-gamma1 pathway.

MeSH Terms

Adult
Apoptosis
Calcium/*metabolism
Cell Line
Cell Survival
Cells, Cultured
Coculture Techniques
Collagen Type I/analysis/*metabolism
Female
Human Umbilical Vein Endothelial Cells
Humans
Muscle, Smooth, Vascular/*cytology/metabolism
Phospholipase C gamma/genetics/*metabolism
Pre-Eclampsia/*blood/*metabolism/pathology
Pregnancy
Protein Kinase C-alpha/metabolism
RNA Interference
*Signal Transduction
Young Adult
Calcium
Collagen Type I
Protein Kinase C-alpha
Phospholipase C gamma