Back to Search
Start Over
Cyclosporin A enhances the ability of trophoblasts to displace the activated human umbilical vein endothelial cell monolayers.
- Source :
-
International journal of clinical and experimental pathology [Int J Clin Exp Pathol] 2013 Oct 15; Vol. 6 (11), pp. 2441-50. Date of Electronic Publication: 2013 Oct 15 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Transformation of the spiral arteries including the displacement of vascular endothelial cells by extravillous trophoblasts is an essential prerequisite to normal placentation. However, the activated endothelial cells resist the invasion of trophoblasts, which contributes to the pathologies of some pregnant disorders. Our previous studies have demonstrated that Cyclosporin A (CsA) promotes the migration and invasion of human first-trimester trophoblasts. In the present study, we further investigated whether CsA could promote the ability of trophoblasts to displace the activated human umbilical vein endothelial cell (HUVEC) monolayers and the possible molecular mechanisms. Human choriocarcinoma Jar cells were used as a model of invasive trophoblasts. CsA pretreated JAR cells (red) were added to HUVEC monolayers (green) activated with either necrotic JAR cells or tumor necrosis factor alpha (TNFα). The ability of JAR cells to displace HUVECs from the monolayers was examined by confocal microscopy. The effects of CsA on Titin and E-cadherin expression, matrix metalloproteinases (MMPs) activity and CXCL12 secretion of JAR cells were evaluated by western blot, gelatin zymography and enzyme-linked immunosorbent assay (ELISA), respectively. We found that CsA pretreatment increased the ability of JAR cells to displace activated HUVECs from the monolayers. However, the displacement was reduced by untreated JAR cells. Moreover, CsA pretreatment up-regulated Titin expression, down-regulated E-cadherin expression, improved MMP2 and MMP9 activity, and increased the CXCL12 secretion in JAR cells. These results indicate that CsA may improve the trophoblast invasion to activated HUVEC monolayers through different downstream targets, and ultimately, improve the transformation and remodeling of spiral arteries.
- Subjects :
- Antigens, CD
Cadherins metabolism
Cell Line, Tumor
Chemokine CXCL12 metabolism
Coculture Techniques
Connectin metabolism
Female
Humans
Matrix Metalloproteinase 2 metabolism
Matrix Metalloproteinase 9 metabolism
Necrosis
Pregnancy
Signal Transduction drug effects
Trophoblasts metabolism
Trophoblasts pathology
Tumor Necrosis Factor-alpha metabolism
Cell Adhesion
Cell Movement drug effects
Cyclosporine pharmacology
Human Umbilical Vein Endothelial Cells metabolism
Placentation drug effects
Trophoblasts drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1936-2625
- Volume :
- 6
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- International journal of clinical and experimental pathology
- Publication Type :
- Academic Journal
- Accession number :
- 24228106