cxcl12cxcr4 axis triggers the activation of egf receptor and erk signaling pathway in csa-induced proliferation of human trophoblast cellscxcl12cxcr4轴触发egf受体的激活和erk信号通路csa-induced人类滋养层细胞的增殖.pdfVIP

CXCL12/CXCR4 Axis Triggers the Activation of EGF Receptor and ERK Signaling Pathway in CsA-Induced Proliferation of Human Trophoblast Cells 1 1 1 1 1 1 Hong-Bo Zhao , Chuan-Ling Tang , Yan-Li Hou , Li-Rong Xue , Ming-Qing Li , Mei-Rong Du , Da- Jin Li1,2* 1 Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China, 2 Department of Obstetrics and Gynecology, the Affiliated Hospital, Hainan Medical College, Haikou, China Abstract Introduction: Our previous study has demonstrated Cyclosporin A (CsA) promotes the proliferation of human trophoblast cells. Therefore, we further investigate the intracellular signaling pathway involved in the CsA-induced proliferation of human trophoblast cells. Methods: Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the regulation of CsA on CXCL12 secretion in human trophoblast cells. Immunofluorescence analysis and western blotting analysis were used to investigate the role of CXCL12/CXCR4 axis in the CsA-induced epidermal growth factor receptor (EGFR) phosphorylation in human trophoblast cells. 5-bromo-2 9-deoxyuridine (BrdU) cell proliferation assay was performed to analyze the involvement of EGFR and its downstream extracellular signal-regulated protein kinase (ERK) signaling pathway in the CsA-induced proliferation of human trophoblast cells. Results: Low concentration of CsA promoted the secretion of CXCL12, and recombinant human CXCL12 promoted the phosphorylation of EGFR in primary human trophoblast cells and choriocarcinoma cell line JEG-3. The inhibition of CXCL12 or CXCR4 by ei