title: Thymic stromal lymphopoietin downregulates NME1 expression and promotes invasion in human trophoblasts via the activation of STAT3 signaling pathway.
abstract: Our previous study has demonstrated that TSLP induces the invasion of human trophoblasts and plays a role in embryo implantation. The present study is undertaken to explore the mechanism by which TSLP modulates trophoblast invasion. It was revealed that TSLP treatment significantly downregulated NME1 and TIMP1 expression in both human trophoblasts and JEG-3 cells. The stimulatory effect of TSLP on trophoblast invasion was partially inhibited by either STAT3 inhibitor or STAT5 inhibitor. The downregulation of NME1 expression by TSLP was completely abrogated by STAT3 inhibitor. TIMP1 expression was attenuated by NME1 siRNA interference and enhanced by NME1 overexpression in JEG-3 cells. TSLP-stimulated increase in trophoblast invasion was partially attenuated by NME1 overexpression. Our data suggest that TSLP might downregulate NME1 expression via STAT3 signaling pathway, affecting TIMP1 expression in influencing trophoblast invasion. Our studies suggest that further studies on TSLP as a potential therapeutic for recurrent spontaneous abortion are warranted.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Deng-Xuan
authors.initials: DX
authors.lastname: Fan
authors.forename: Jie
authors.initials: J
authors.lastname: Duan
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Zhu
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jin
mesh_terms: D000328:Adult; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D054778:NM23 Nucleoside Diphosphate Kinases; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C517938:NME1 protein, human; D000094632:Thymic Stromal Lymphopoietin