CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties
| Autor: | Manuela Wuelling, Diana Klein, Alexandra Gellhaus, Manuela Kirsch, Friederike Kipkeew, Elke Winterhager |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cyclin-Dependent Kinase Inhibitor p21 medicine.medical_specialty Medizin Review Biology Models Biological Cell Line 03 medical and health sciences Cellular and Molecular Neuroscience Nephroblastoma Overexpressed Protein 0302 clinical medicine Downregulation and upregulation Cell Movement Internal medicine Placenta medicine Humans Phosphorylation Extracellular Signal-Regulated MAP Kinases reproductive and urinary physiology Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 Cell Proliferation integumentary system Receptors Notch Cell growth Decidua Trophoblast Cell Biology Cell Cycle Checkpoints Cell cycle beta-Galactosidase Cell biology Trophoblasts Up-Regulation 030104 developmental biology medicine.anatomical_structure Endocrinology 030220 oncology & carcinogenesis CYR61 Focal Adhesion Protein-Tyrosine Kinases embryonic structures G1 phase Proto-Oncogene Proteins c-akt Biomarkers Cysteine-Rich Protein 61 Signal Transduction |
| Popis: | During placental development, continuous invasion of trophoblasts into the maternal compartment depends on the support of proliferating extravillous trophoblasts (EVTs). Unlike tumor cells, EVTs escape from the cell cycle before invasion into the decidua and spiral arteries. This study focused on the regulation properties of glycosylated and non-glycosylated matricellular CCN1 and CCN3, primarily for proliferation control in the benign SGHPL-5 trophoblast cell line, which originates from the first-trimester placenta. Treating SGHPL-5 trophoblast cells with the glycosylated forms of recombinant CCN1 and CCN3 decreased cell proliferation by bringing about G0/G1 cell cycle arrest, which was accompanied by the upregulation of activated Notch-1 and its target gene p21. Interestingly, both CCN proteins increased senescence-associated β-galactosidase activity and the expression of the senescence marker p16. The migration capability of SGHPL-5 cells was mostly enhanced in response to CCN1 and CCN3, by the activation of FAK and Akt kinase but not by the activation of ERK1/2. In summary, both CCN proteins play a key role in regulating trophoblast cell differentiation by inducing senescence and enhancing migration properties. Reduced levels of CCN1 and CCN3, as found in early-onset preeclampsia, could contribute to a shift from invasive to proliferative EVTs and may explain their shallow invasion properties in this disease. |
| Databáze: | OpenAIRE |
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