title: Preeclampsia serum-induced collagen I expression and intracellular calcium levels in arterial smooth muscle cells are mediated by the PLC-γ1 pathway.
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-γ1-1,4,5-trisphosphate (PLC-γ1-IP3) signaling, thereby increasing protein kinase C-α (PKC-α) activity, collagen I expression and intracellular Ca(2+) concentrations ([Ca(2+)]i) in human umbilical artery smooth muscle cells (HUASMCs). HUASMCs and HUVECs were cocultured with normal or PE sera before PLC-γ1 silencing. Increased PLC-γ1 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-γ1 silencing. Compared with normal sera, PE sera increased [Ca(2+)]i in cocultured HUASMCs (P<0.05), which was inhibited by PLC-γ1 and IP3R silencing. Finally, PE sera-induced PKC-α activity and collagen I expression was inhibited by PLC-γ1 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-γ1, 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 [Ca(2+)]i and induced PKC-α activation and collagen I expression in cocultured HUASMCs via the PLC-γ1 pathway.
authors.affiliation: Obstetric Intensive Care Center, The Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Rongzhen
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Obstetric Intensive Care Center, The Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yincheng
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Obstetric Intensive Care Center, The Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Obstetric Intensive Care Center, The Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Gu
authors.affiliation: Obstetric Intensive Care Center, The Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Obstetric Intensive Care Center, The Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Obstetric Intensive Care Center, The Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yuedi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000328:Adult; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000032:analysis / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood* / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D051571:Protein Kinase C-alpha / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D051571:Protein Kinase C-alpha; D051966:Phospholipase C gamma; D002118:Calcium