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Gαq-PKD/PKCμ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy
Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a successful pregnancy in human. Here, we demonstrated that knockout of Gαq lead to an aberrantly enhanced inflammatory state during decidua...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374280/ https://www.ncbi.nlm.nih.gov/pubmed/37498654 http://dx.doi.org/10.7554/eLife.83083 |
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author | Jiang, Yufei He, Yan Liu, Songting Li, Gaizhen Chen, Dunjin Deng, Wenbo Li, Ping Zhang, Ying Wu, Jinxiang Li, Jianing Wang, Longmei Lin, Jiajing Wang, Haibin Kong, Shuangbo Shi, Guixiu |
author_facet | Jiang, Yufei He, Yan Liu, Songting Li, Gaizhen Chen, Dunjin Deng, Wenbo Li, Ping Zhang, Ying Wu, Jinxiang Li, Jianing Wang, Longmei Lin, Jiajing Wang, Haibin Kong, Shuangbo Shi, Guixiu |
author_sort | Jiang, Yufei |
collection | PubMed |
description | Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a successful pregnancy in human. Here, we demonstrated that knockout of Gαq lead to an aberrantly enhanced inflammatory state during decidualization. Furthermore, we showed that deficiency of Gαq resulted in over-activation of nuclear factor (NF)-κB signaling, due to the decreased expression of NFκBIA, which encode the IκB protein and is the negative regulator for NF-κB. Mechanistically, Gαq deficiency decreased the Protein kinase D (PKD, also called PKCμ) phosphorylation levels, leading to attenuated HDAC5 phosphorylation and thus its nuclear export. Aberrantly high level of nuclear HDAC5 retarded histone acetylation to inhibit the induced NFκBIA transcription during decidualization. Consistently, pharmacological activation of the PKD/PKCμ or inhibition of the HDAC5 restored the inflammatory state and proper decidual response. Finally, we disclosed that over-active inflammatory state in Gαq-deficient decidua deferred the blastocyst hatching and adhesion in vitro, and the decidual expression of Gαq was significantly lower in women with recurrent pregnancy loss compared with normal pregnancy. In brief, we showed here that Gαq as a key regulator of the inflammatory cytokine’s expression and decidual homeostasis in response to differentiation cues, which is required for successful implantation and early pregnancy. |
format | Online Article Text |
id | pubmed-10374280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-103742802023-07-28 Gαq-PKD/PKCμ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy Jiang, Yufei He, Yan Liu, Songting Li, Gaizhen Chen, Dunjin Deng, Wenbo Li, Ping Zhang, Ying Wu, Jinxiang Li, Jianing Wang, Longmei Lin, Jiajing Wang, Haibin Kong, Shuangbo Shi, Guixiu eLife Cell Biology Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a successful pregnancy in human. Here, we demonstrated that knockout of Gαq lead to an aberrantly enhanced inflammatory state during decidualization. Furthermore, we showed that deficiency of Gαq resulted in over-activation of nuclear factor (NF)-κB signaling, due to the decreased expression of NFκBIA, which encode the IκB protein and is the negative regulator for NF-κB. Mechanistically, Gαq deficiency decreased the Protein kinase D (PKD, also called PKCμ) phosphorylation levels, leading to attenuated HDAC5 phosphorylation and thus its nuclear export. Aberrantly high level of nuclear HDAC5 retarded histone acetylation to inhibit the induced NFκBIA transcription during decidualization. Consistently, pharmacological activation of the PKD/PKCμ or inhibition of the HDAC5 restored the inflammatory state and proper decidual response. Finally, we disclosed that over-active inflammatory state in Gαq-deficient decidua deferred the blastocyst hatching and adhesion in vitro, and the decidual expression of Gαq was significantly lower in women with recurrent pregnancy loss compared with normal pregnancy. In brief, we showed here that Gαq as a key regulator of the inflammatory cytokine’s expression and decidual homeostasis in response to differentiation cues, which is required for successful implantation and early pregnancy. eLife Sciences Publications, Ltd 2023-07-27 /pmc/articles/PMC10374280/ /pubmed/37498654 http://dx.doi.org/10.7554/eLife.83083 Text en © 2023, Jiang, He et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Jiang, Yufei He, Yan Liu, Songting Li, Gaizhen Chen, Dunjin Deng, Wenbo Li, Ping Zhang, Ying Wu, Jinxiang Li, Jianing Wang, Longmei Lin, Jiajing Wang, Haibin Kong, Shuangbo Shi, Guixiu Gαq-PKD/PKCμ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy |
title | Gαq-PKD/PKCμ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy |
title_full | Gαq-PKD/PKCμ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy |
title_fullStr | Gαq-PKD/PKCμ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy |
title_full_unstemmed | Gαq-PKD/PKCμ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy |
title_short | Gαq-PKD/PKCμ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy |
title_sort | gαq-pkd/pkcμ signal regulating the nuclear export of hdac5 to induce the iκb expression and limit the nf-κb-mediated inflammatory response essential for early pregnancy |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374280/ https://www.ncbi.nlm.nih.gov/pubmed/37498654 http://dx.doi.org/10.7554/eLife.83083 |
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