The Globular Heads of the C1q Receptor Regulate Apoptosis in Human Extravillous Cytotrophoblast-derived Transformed Cells via a Mitochondria-dependent Pathway
Article first published online: 12 SEP 2013
© 2013 John Wiley & Sons Ltd
American Journal of Reproductive Immunology
Volume 71, Issue 1, pages 73–85, January 2014
How to Cite
The globular heads of the C1q receptor regulate apoptosis in human extravillous cytotrophoblast-derived transformed cells via a mitochondria-dependent pathway. Am J Reprod Immunol 2014; 71: 73–85, , , , , .
- Issue published online: 11 DEC 2013
- Article first published online: 12 SEP 2013
- Manuscript Accepted: 15 AUG 2013
- Manuscript Received: 28 MAR 2013
- National Natural Science Foundation of China. Grant Number: 81000251
- Nanjing Medical Science and Technique Development Foundation. Grant Number: QRX11112
- extravillous cytotrophoblast (EVCT);
- receptor for the globular heads of the human C1q (gC1qR)
The receptor for the globular head of human C1q (gC1qR) predominantly localizes to the mitochondrial matrix. gC1qR mediates many biological responses, including growth perturbations, morphological abnormalities and the initiation of apoptosis. The purpose of this study was to investigate the relationship between gC1qR expression, mitochondrial dysfunction and the regulation of apoptosis in human extravillous cytotrophoblast (EVCT)-derived transformed cell lines (HTR-8/SVneo and HPT-8).
Method of study
gC1qR expression was examined in human placental villi using real-time qPCR and Western blot analysis. The apoptotic death of HTR-8/SVneo and HPT-8 cells was assessed using flow cytometric analysis. Mitochondrial function was assessed via ROS generation, the amount of cytosolic Ca2+ and changes in the mitochondrial membrane potential (Δψm).
The expression of the gC1qR gene was significantly increased in spontaneous abortion samples relative to induced abortion samples. HTR-8/SVneo and HPT-8 cells transfected with a gC1qR vector showed upregulation of cellular apoptosis and mitochondrial dysfunction, interestingly, which were abrogated by the addition of metformin. Metformin may protect mitochondrial function.
These data support a mechanism whereby gC1qR induces apoptosis through mitochondria-dependent pathways in human EVCT-derived transformed cells.