Primary Cilia in Trophoblastic Cells: Potential Involvement in Preeclampsia
| Autor: | Samira Catharina Hoock, Annemarie Neuhoff, Frank Louwen, Alice Steglich Souto, Christine Eichbaum, Alexandra Friemel, Juping Yuan, Susanne Roth, Andreas Ritter, Qi Chen, Nina-Naomi Kreis, Christine Solbach |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Placental growth factor Adult Vascular Endothelial Growth Factor A Placenta Biology Cell Line 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Pre-Eclampsia Intraflagellar transport Pregnancy Internal Medicine medicine Humans Hedgehog Proteins Cilia reproductive and urinary physiology Placenta Growth Factor Tube formation Interleukin-6 Tumor Necrosis Factor-alpha Cilium Placentation Trophoblast female genital diseases and pregnancy complications Matrix Metalloproteinases Cell biology Trophoblasts Vascular endothelial growth factor 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis embryonic structures Female Signal transduction Signal Transduction |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 76(5) |
| ISSN: | 1524-4563 |
| Popis: | The pathogenesis of preeclampsia, a pregnancy-related disease, is not completely understood. The primary cilium transduces a diverse array of signaling pathways important for vital cellular activities. Primary cilia were reported to facilitate trophoblastic cell invasion. We hypothesized their further functions in trophoblasts and were interested in related molecular mechanisms. We systematically examined the presence, length and percentage of the primary cilium, its mediated signal transduction, and its connection to trophoblast function. Various cellular and molecular methods were used including immunofluorescence staining, spheroid formation, gene analysis, invasion and tube formation assays with trophoblastic cell lines, primary trophoblasts, and placental tissues. We show that primary cilia are present in various trophoblastic cell lines derived from first trimester placentas. Cilia are also observable in primary trophoblasts, though in a small quantity. Importantly, primary cilia are shortened in trophoblastic cells derived from preeclamptic placentas. Mechanistically, interleukin-6, tumor necrosis factor-α or sera from patients with preeclampsia are able to reduce the length of primary cilia and impair the important sonic hedgehog signaling pathway. Functionally, trophoblastic cells with defective cilia display severe failures in their key functions, like migration, invasion and tube formation, also observed in trophoblastic cells depleted of the intraflagellar transport protein 88. This is accompanied by reduced gene expression of matrix metallopeptidases, vascular endothelial growth factor, and placental growth factor. This work highlights the significance of primary cilia in the functions of trophoblastic cells. Dysfunctional cilia may lead to compromised migration, invasion, and endothelial remodeling of trophoblastic cells, contributing to the development of preeclampsia. |
| Databáze: | OpenAIRE |
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