Preeclampsia serum-induced collagen I expression and intracellular calcium levels in arterial smooth muscle cells are mediated by the PLC-gamma1 pathway.
- Author:
Rongzhen JIANG
1
;
Yincheng TENG
;
Yajuan HUANG
;
Jinghong GU
;
Li MA
;
Ming LI
;
Yuedi ZHOU
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH: 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
- From:Experimental & Molecular Medicine 2014;46(9):e115-
- CountryRepublic of Korea
- Language:English
- 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.
