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Cyclosporin A alleviates trophoblast apoptosis and senescence by promoting autophagy in preeclampsia.

Authors :
Hu H
Chen W
Tao Z
Li Z
He J
Peng Y
Ma J
Wen H
Li J
Wang X
Zhong M
Source :
Placenta [Placenta] 2022 Jan; Vol. 117, pp. 95-108. Date of Electronic Publication: 2021 Nov 12.
Publication Year :
2022

Abstract

Introduction: 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.<br />Methods: 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).<br />Results: 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.<br />Discussion: CsA may display some therapeutic effects against PE by activating autophagy in vivo and in vitro.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1532-3102
Volume :
117
Database :
MEDLINE
Journal :
Placenta
Publication Type :
Academic Journal
Accession number :
34785431
Full Text :
https://doi.org/10.1016/j.placenta.2021.11.003