Back to Search
Start Over
Cyclosporin A alleviates trophoblast apoptosis and senescence by promoting autophagy in preeclampsia.
- Source :
- Placenta; Jan2022, Vol. 117, p95-108, 14p
- Publication Year :
- 2022
-
Abstract
- <bold>Introduction: </bold>Abnormal extravillous trophoblast (EVT) function is closely related to preeclampsia (PE) and may be caused by inadequate autophagy, apoptosis, and senescence. Cyclosporin A (CsA) is an effective immunosuppressant that has been reported to stimulate autophagy and exert benign biological effects on EVTs. Therefore, we hypothesized that CsA may display therapeutic efficacy against PE by activating autophagy.<bold>Methods: </bold>We established the nitro-l-arginine methyl ester (l-NAME)-induced preeclamptic mice model and a hypoxia-reoxygenation (H/R) model in vitro. The effects of CsA on autophagy were evaluated by western blotting (WB). The effects of CsA on apoptosis were analyzed by Hematoxylin-eosin (H&E) staining, cell apoptosis assay and WB. Senescence-associated β-galactosidase (SA-β-gal) staining, RT-qPCR and WB were used to examine the senescence level. RT-qPCR were used to detect the senescence-associated secretory phenotype (SASP) level. DCFH-DA fluorescent probe, dihydroethidium (DHE) staining and mitochondrial membrane potential (ΔΨm) were used to detect senescence-associated mitochondrial dysfunction (SAMD).<bold>Results: </bold>CsA alleviated PE-like symptoms and reduced placental necrosis and senescence in mice injected with l-NAME. CsA ameliorated placental SASP and SAMD level induced by l-NAME. CsA also upregulated the expression of autophagic proteins in mouse placentas disrupted using l-NAME. In vitro, we found that CsA reversed H/R-induced apoptosis and senescence, as well as decreasing SASP and SAMD levels and upregulating autophagic proteins levels. Notably, 3-methyladenine (3-MA), an early phase inhibitor of autophagosome formation, abolished the protective effects of CsA against H/R.<bold>Discussion: </bold>CsA may display some therapeutic effects against PE by activating autophagy in vivo and in vitro. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01434004
- Volume :
- 117
- Database :
- Supplemental Index
- Journal :
- Placenta
- Publication Type :
- Academic Journal
- Accession number :
- 154563718
- Full Text :
- https://doi.org/10.1016/j.placenta.2021.11.003