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Adenoviral mediated expression of anti-inflammatory progranulin by placental explants modulates endothelial cell
Johannes Stubert1, Marlen Szewczyk1, Alf Spitschak2
1Department of Obstetrics and Gynecology, Rostock University Medical Center, Suedring 81, 18059, Rostock, Germany.
Placenta
|February 15, 2020
Summary
Preeclampsia involves trophoblast dysfunction. Placental progranulin, an anti-inflammatory cytokine, was investigated for its role in endothelial cell activation, showing it partially reverses increased ICAM-1 expression.
Area of Science:
- Reproductive biology
- Immunology
- Cell biology
Background:
- Preeclampsia is linked to placental dysfunction and endothelial activation.
- Progranulin (PGRN) is an anti-inflammatory cytokine with potential roles in pregnancy complications.
Purpose of the Study:
- To investigate the impact of placental progranulin synthesis on endothelial cell activation in the context of preeclampsia.
Main Methods:
- Adenoviral vectors were used to modify placental progranulin expression in human placental explants.
- Primary human umbilical venous endothelial cells (HUVECs) were treated with conditioned media.
- HUVEC functional assays included proliferation, viability, cytotoxicity, and analysis of ICAM-1 and E-selectin expression.
Main Results:
- Adenoviral-mediated overexpression of progranulin (Ad.PGRN) significantly increased placental progranulin levels.
- Conditioned media from placental explants increased HUVEC cytotoxicity, reduced proliferation and viability, and elevated ICAM-1 and E-selectin expression.
- Overexpression of progranulin antagonized the increase in Intercellular adhesion molecule-1 (ICAM-1) expression induced by conditioned media, but did not affect other parameters.
Conclusions:
- Placental progranulin up-regulation may serve as an endogenous anti-inflammatory mechanism.
- Progranulin partially counteracts endothelial cell activation, specifically ICAM-1 expression, during preeclampsia.
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