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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
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.
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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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