Reference - Detail
| RRC ID | 67682 |
|---|---|
| Author | Zhou Z, Wang R, Yang X, Lu XY, Zhang Q, Wang YL, Wang H, Zhu C, Lin HY, Wang H. |
| Title | The cAMP-responsive element binding protein (CREB) transcription factor regulates furin expression during human trophoblast syncytialization. |
| Journal | Placenta |
| Abstract |
INTRODUCTION:The multinucleated syncytiotrophoblast is formed and maintained by cytotrophoblast cell fusion and serves multiple functions to ensure a successful pregnancy. We have previously reported that the proprotein convertase furin is required for trophoblast syncytialization by processing type 1 insulin-like growth factor receptor (IGF1R). METHODS:Utilizing trophoblast cell fusion models including induced fusion of choriocarcinoma BeWo cells and spontaneous fusion of primary cultured term cytotrophoblast cells, the expression of furin was evaluated by quantitative real-time PCR, Western blotting and immunofluorescence. The key transcription factor regulating the FUR gene promoter and critical responsive elements were identified by luciferase reporter assays, truncated mutants analysis, site-directed mutagenesis and ChIP. RESULTS:We demonstrated that the levels of FUR mRNA were significantly stimulated by cAMP/PKA signaling pathway during spontaneous fusion of cytotrophoblast cells and forskolin-induced fusion of BeWo cells. cAMP-responsive element binding protein (CREB) was proven to be the key transcription factor which regulated the FUR P1 promoter during forskolin-induced BeWo cell fusion, and two critical cAMP-responsive elements (CREs) in the P1 promoter were further identified. Finally, we showed that CREB mediated endogenous furin activation and that CREB siRNA attenuated forskolin-induced furin expression and cell fusion in BeWo cells. DISCUSSION:This provides the first evidence of the upstream regulator of furin during trophoblast cell fusion. CONCLUSIONS:The above results suggest that the FUR transcription is activated by CREB-dependent stimulation of the FUR P1 promoter during human trophoblast syncytialization. |
| Volume | 35(11) |
| Pages | 907-18 |
| Published | 2014-11-1 |
| DOI | 10.1016/j.placenta.2014.07.017 |
| PII | S0143-4004(14)00644-4 |
| PMID | 25175744 |
| MeSH | Cell Fusion Cell Line, Tumor Cyclic AMP Response Element-Binding Protein / metabolism* Cyclic AMP-Dependent Protein Kinases / metabolism Furin / metabolism* Gene Expression Regulation, Developmental* HEK293 Cells Humans Promoter Regions, Genetic Signal Transduction Trophoblasts / physiology* |
| IF | 3.177 |
| Resource | |
| DNA material | CSII-CMV-MCS-IRES2-Venus (RDB04383) |