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Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway

Dysregulated biological behaviors of trophoblast cells can result in recurrent spontaneous abortion (RSA)—whose underlying etiology still remains insufficient. Autophagy, a conserved intracellular physiological process, is precisely monitored throughout whole pregnancy. Although the exact mechanism...

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Autores principales: Wang, Peixin, Zhao, Chenqiong, Zhou, Hanjing, Huang, Xiaona, Ying, Hanqi, Zhang, Songying, Pan, Yibin, Zhu, Haiyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418899/
https://www.ncbi.nlm.nih.gov/pubmed/37569278
http://dx.doi.org/10.3390/ijms241511899
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author Wang, Peixin
Zhao, Chenqiong
Zhou, Hanjing
Huang, Xiaona
Ying, Hanqi
Zhang, Songying
Pan, Yibin
Zhu, Haiyan
author_facet Wang, Peixin
Zhao, Chenqiong
Zhou, Hanjing
Huang, Xiaona
Ying, Hanqi
Zhang, Songying
Pan, Yibin
Zhu, Haiyan
author_sort Wang, Peixin
collection PubMed
description Dysregulated biological behaviors of trophoblast cells can result in recurrent spontaneous abortion (RSA)—whose underlying etiology still remains insufficient. Autophagy, a conserved intracellular physiological process, is precisely monitored throughout whole pregnancy. Although the exact mechanism or role remains elusive, epigenetic modification has emerged as an important process. Herein, we found that a proportion of RSA patients exhibited higher levels of autophagy in villus tissues compared to controls, accompanied with impaired histone deacetylase (HDAC) expression. The purpose of this study is to explore the connection between HDACs and autophagy in the pathological course of RSA. Mechanistically, using human trophoblast cell models, treatment with HDAC inhibitor (HDACI)-trichostatin A (TSA) can induce autophagy by promoting nuclear translocation and transcriptional activity of the central autophagic regulator transcription factor EB (TFEB). Specifically, overactivated autophagy is involved in the TSA-driven growth inhibition of trophoblast, which can be partially reversed by the autophagy inhibitor chloroquine (CQ) or RNA interference of TFEB. In summary, our results reveal that abnormal acetylation and autophagy levels during early gestation may be associated with RSA and suggest the potential novel molecular target TFEB for RSA treatment.
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spelling pubmed-104188992023-08-12 Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway Wang, Peixin Zhao, Chenqiong Zhou, Hanjing Huang, Xiaona Ying, Hanqi Zhang, Songying Pan, Yibin Zhu, Haiyan Int J Mol Sci Article Dysregulated biological behaviors of trophoblast cells can result in recurrent spontaneous abortion (RSA)—whose underlying etiology still remains insufficient. Autophagy, a conserved intracellular physiological process, is precisely monitored throughout whole pregnancy. Although the exact mechanism or role remains elusive, epigenetic modification has emerged as an important process. Herein, we found that a proportion of RSA patients exhibited higher levels of autophagy in villus tissues compared to controls, accompanied with impaired histone deacetylase (HDAC) expression. The purpose of this study is to explore the connection between HDACs and autophagy in the pathological course of RSA. Mechanistically, using human trophoblast cell models, treatment with HDAC inhibitor (HDACI)-trichostatin A (TSA) can induce autophagy by promoting nuclear translocation and transcriptional activity of the central autophagic regulator transcription factor EB (TFEB). Specifically, overactivated autophagy is involved in the TSA-driven growth inhibition of trophoblast, which can be partially reversed by the autophagy inhibitor chloroquine (CQ) or RNA interference of TFEB. In summary, our results reveal that abnormal acetylation and autophagy levels during early gestation may be associated with RSA and suggest the potential novel molecular target TFEB for RSA treatment. MDPI 2023-07-25 /pmc/articles/PMC10418899/ /pubmed/37569278 http://dx.doi.org/10.3390/ijms241511899 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Peixin
Zhao, Chenqiong
Zhou, Hanjing
Huang, Xiaona
Ying, Hanqi
Zhang, Songying
Pan, Yibin
Zhu, Haiyan
Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway
title Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway
title_full Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway
title_fullStr Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway
title_full_unstemmed Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway
title_short Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway
title_sort dysregulation of histone deacetylases inhibits trophoblast growth during early placental development partially through tfeb-dependent autophagy-lysosomal pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418899/
https://www.ncbi.nlm.nih.gov/pubmed/37569278
http://dx.doi.org/10.3390/ijms241511899
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