Cargando…

Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals

Survival of the conceptus is dependent on continuous progesterone signaling in the maternal decidua but how this is achieved under conditions of oxidative stress that characterize early pregnancy is unknown. Using primary cultures, we show that modest levels of reactive oxygen species (ROS) increase...

Descripción completa

Detalles Bibliográficos
Autores principales: Leitao, Beatriz, Jones, Marius C., Fusi, Luca, Higham, Jenny, Lee, Yun, Takano, Masashi, Goto, Tomoko, Christian, Mark, Lam, Eric W.-F., Brosens, Jan J.
Formato: Texto
Lenguaje:English
Publicado: The Federation of American Societies for Experimental Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857868/
https://www.ncbi.nlm.nih.gov/pubmed/20026682
http://dx.doi.org/10.1096/fj.09-149153
_version_ 1782180356596695040
author Leitao, Beatriz
Jones, Marius C.
Fusi, Luca
Higham, Jenny
Lee, Yun
Takano, Masashi
Goto, Tomoko
Christian, Mark
Lam, Eric W.-F.
Brosens, Jan J.
author_facet Leitao, Beatriz
Jones, Marius C.
Fusi, Luca
Higham, Jenny
Lee, Yun
Takano, Masashi
Goto, Tomoko
Christian, Mark
Lam, Eric W.-F.
Brosens, Jan J.
author_sort Leitao, Beatriz
collection PubMed
description Survival of the conceptus is dependent on continuous progesterone signaling in the maternal decidua but how this is achieved under conditions of oxidative stress that characterize early pregnancy is unknown. Using primary cultures, we show that modest levels of reactive oxygen species (ROS) increase sumoylation in human endometrial stromal cells (HESCs), leading to enhanced modification and transcriptional inhibition of the progesterone receptor (PR). The ability of ROS to induce a sustained hypersumoylation response, or interfere with PR activity, was lost upon differentiation of HESCs into decidual cells. Hypersumoylation in response to modest levels of ROS requires activation of the JNK pathway. Although ROS-dependent JNK signaling is disabled on decidualization, the cells continue to mount a transcriptional response, albeit distinct from that observed in undifferentiated HESCs. We further show that attenuated JNK signaling in decidual cells is a direct consequence of altered expression of key pathway modulators, including induction of MAP kinase phosphatase 1 (MKP1). Overexpression of MKP1 dampens JNK signaling, prevents hypersumoylation, and maintains PR activity in undifferentiated HESCs exposed to ROS. Thus, JNK silencing uncouples ROS signaling from the SUMO conjugation pathway and maintains progesterone responses and cellular homeostasis in decidual cells under oxidative stress conditions imposed by pregnancy.—Leitao, B., Jones, M. C., Fusi, L., Higham, J., Lee, Y. Takano, M., Goto, T., Christian, M., Lam, E. W.-F., Brosens, J. J. Silencing of the Jnk pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals.
format Text
id pubmed-2857868
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher The Federation of American Societies for Experimental Biology
record_format MEDLINE/PubMed
spelling pubmed-28578682010-05-06 Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals Leitao, Beatriz Jones, Marius C. Fusi, Luca Higham, Jenny Lee, Yun Takano, Masashi Goto, Tomoko Christian, Mark Lam, Eric W.-F. Brosens, Jan J. FASEB J Research Communications Survival of the conceptus is dependent on continuous progesterone signaling in the maternal decidua but how this is achieved under conditions of oxidative stress that characterize early pregnancy is unknown. Using primary cultures, we show that modest levels of reactive oxygen species (ROS) increase sumoylation in human endometrial stromal cells (HESCs), leading to enhanced modification and transcriptional inhibition of the progesterone receptor (PR). The ability of ROS to induce a sustained hypersumoylation response, or interfere with PR activity, was lost upon differentiation of HESCs into decidual cells. Hypersumoylation in response to modest levels of ROS requires activation of the JNK pathway. Although ROS-dependent JNK signaling is disabled on decidualization, the cells continue to mount a transcriptional response, albeit distinct from that observed in undifferentiated HESCs. We further show that attenuated JNK signaling in decidual cells is a direct consequence of altered expression of key pathway modulators, including induction of MAP kinase phosphatase 1 (MKP1). Overexpression of MKP1 dampens JNK signaling, prevents hypersumoylation, and maintains PR activity in undifferentiated HESCs exposed to ROS. Thus, JNK silencing uncouples ROS signaling from the SUMO conjugation pathway and maintains progesterone responses and cellular homeostasis in decidual cells under oxidative stress conditions imposed by pregnancy.—Leitao, B., Jones, M. C., Fusi, L., Higham, J., Lee, Y. Takano, M., Goto, T., Christian, M., Lam, E. W.-F., Brosens, J. J. Silencing of the Jnk pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals. The Federation of American Societies for Experimental Biology 2010-05 /pmc/articles/PMC2857868/ /pubmed/20026682 http://dx.doi.org/10.1096/fj.09-149153 Text en © 2010 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Communications
Leitao, Beatriz
Jones, Marius C.
Fusi, Luca
Higham, Jenny
Lee, Yun
Takano, Masashi
Goto, Tomoko
Christian, Mark
Lam, Eric W.-F.
Brosens, Jan J.
Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals
title Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals
title_full Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals
title_fullStr Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals
title_full_unstemmed Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals
title_short Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals
title_sort silencing of the jnk pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals
topic Research Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857868/
https://www.ncbi.nlm.nih.gov/pubmed/20026682
http://dx.doi.org/10.1096/fj.09-149153
work_keys_str_mv AT leitaobeatriz silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals
AT jonesmariusc silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals
AT fusiluca silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals
AT highamjenny silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals
AT leeyun silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals
AT takanomasashi silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals
AT gototomoko silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals
AT christianmark silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals
AT lamericwf silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals
AT brosensjanj silencingofthejnkpathwaymaintainsprogesteronereceptoractivityindecidualizinghumanendometrialstromalcellsexposedtooxidativestresssignals