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Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB

Placental trophoblast apoptosis is a major pathological feature of preeclampsia. Fas has been reported to be highly expressed in the placentas of patients with preeclampsia. However, the role and underlying mechanisms of Fas in the pathogenesis of preeclampsia have not been elucidated. In the presen...

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Autores principales: Lan, Ruihong, Yang, Yang, Song, Jie, Wang, Ling, Gong, Humin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353647/
https://www.ncbi.nlm.nih.gov/pubmed/34434269
http://dx.doi.org/10.3892/etm.2021.10489
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author Lan, Ruihong
Yang, Yang
Song, Jie
Wang, Ling
Gong, Humin
author_facet Lan, Ruihong
Yang, Yang
Song, Jie
Wang, Ling
Gong, Humin
author_sort Lan, Ruihong
collection PubMed
description Placental trophoblast apoptosis is a major pathological feature of preeclampsia. Fas has been reported to be highly expressed in the placentas of patients with preeclampsia. However, the role and underlying mechanisms of Fas in the pathogenesis of preeclampsia have not been elucidated. In the present study, the expression of Fas in JAR human choriocarcinoma cells was overexpressed and knocked down to determine the function and possible mechanism of Fas in trophoblast cells in the progression of preeclampsia. The results of flow cytometry, Cell Counting Kit-8 and Transwell assays indicated that the overexpression of Fas promoted apoptosis, suppressed viability and impaired the migration of the human trophoblast cells. In addition, western blotting revealed that the overexpression of Fas increased the expression of nuclear factor kB (NF-kB), Bax, tumor necrosis factor α (TNF-α) and interleukin-2 (IL-2), and decreased the expression of Bcl-2 at the protein level in trophoblast cells. By contrast, the knockdown of Fas decreased the apoptosis of trophoblast cells and increased their viability and migration. In addition, the knockdown of Fas suppressed the expression of NF-κB, Bax, TNF-α and IL-2, and increased the expression of Bcl-2. Notably, the overexpression of NF-κB p65 attenuated the Fas knockdown-induced inhibition of apoptosis and acceleration of migration of the trophoblast cells. The overexpression of NF-κB in trophoblast cells also reversed the reduction in Bax expression and increase in Bcl-2 expression induced by Fas knockdown in trophoblast cells. These results indicate that Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB, which suggests that the silencing of Fas is a promising therapeutic strategy for preeclampsia.
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spelling pubmed-83536472021-08-24 Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB Lan, Ruihong Yang, Yang Song, Jie Wang, Ling Gong, Humin Exp Ther Med Articles Placental trophoblast apoptosis is a major pathological feature of preeclampsia. Fas has been reported to be highly expressed in the placentas of patients with preeclampsia. However, the role and underlying mechanisms of Fas in the pathogenesis of preeclampsia have not been elucidated. In the present study, the expression of Fas in JAR human choriocarcinoma cells was overexpressed and knocked down to determine the function and possible mechanism of Fas in trophoblast cells in the progression of preeclampsia. The results of flow cytometry, Cell Counting Kit-8 and Transwell assays indicated that the overexpression of Fas promoted apoptosis, suppressed viability and impaired the migration of the human trophoblast cells. In addition, western blotting revealed that the overexpression of Fas increased the expression of nuclear factor kB (NF-kB), Bax, tumor necrosis factor α (TNF-α) and interleukin-2 (IL-2), and decreased the expression of Bcl-2 at the protein level in trophoblast cells. By contrast, the knockdown of Fas decreased the apoptosis of trophoblast cells and increased their viability and migration. In addition, the knockdown of Fas suppressed the expression of NF-κB, Bax, TNF-α and IL-2, and increased the expression of Bcl-2. Notably, the overexpression of NF-κB p65 attenuated the Fas knockdown-induced inhibition of apoptosis and acceleration of migration of the trophoblast cells. The overexpression of NF-κB in trophoblast cells also reversed the reduction in Bax expression and increase in Bcl-2 expression induced by Fas knockdown in trophoblast cells. These results indicate that Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB, which suggests that the silencing of Fas is a promising therapeutic strategy for preeclampsia. D.A. Spandidos 2021-10 2021-07-23 /pmc/articles/PMC8353647/ /pubmed/34434269 http://dx.doi.org/10.3892/etm.2021.10489 Text en Copyright: © Lan et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Lan, Ruihong
Yang, Yang
Song, Jie
Wang, Ling
Gong, Humin
Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB
title Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB
title_full Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB
title_fullStr Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB
title_full_unstemmed Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB
title_short Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB
title_sort fas regulates the apoptosis and migration of trophoblast cells by targeting nf-κb
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353647/
https://www.ncbi.nlm.nih.gov/pubmed/34434269
http://dx.doi.org/10.3892/etm.2021.10489
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