The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells

Autores
Fernández, Laura del Carmen; Kong, Chow Seng; Alkhoury, Majd; Tryfonos, Maria; Brighton, Paul J.; Rawlings, Thomas M.; Muter, Joanne; Gori, María Soledad; Perez Leiros, Claudia; Lucas, Emma S.; Brosens, Jan J.; Ramhorst, Rosanna Elizabeth
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Decidualization denotes the process of inflammatory reprogramming of endometrial stromal cells (EnSC) into specialized decidual cells (DC). During this process, EnSC are subjected to endoplasmic reticulum (ER) stress as well as acute cellular senescence. Both processes contribute to the proinflammatory mid-luteal implantation window and their dysregulation has been implicated in reproductive failure. Here, we evaluated the link between ER stress, decidual differentiation and senescence. In-silico analysis identified HSPA5 gene, codifying the ER chaperone BiP, as a potentially critical regulator of cell fate divergence of decidualizing EnSC into anti-inflammatory DC and pro-inflammatory senescent decidual cells (snDC). Knockdown of HSPA5 in primary EnSC resulted both in decreased expression of DC marker genes and attenuated induction of senescence associated β-galactosidase activity, a marker of snDC. Stalling of the decidual reaction upon HSPA5 knockdown was apparent at 8 days of differentiation and was preceded by the upregulation of ER stress associated proteins IRE1α and PERK. Further, HSPA5 knockdown impaired colony-forming unit activity of primary EnSC, indicative of loss of cellular plasticity. Together, our results point to a key role for HSPA5/BiP in decidual transformation of EnSCs and highlight the importance of constraining ER stress levels during this process.
Fil: Fernández, Laura del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. University of Warwick; Reino Unido
Fil: Kong, Chow Seng. University of Warwick; Reino Unido
Fil: Alkhoury, Majd. University Hospitals Coventry and Warwickshire NHS Trust; Reino Unido
Fil: Tryfonos, Maria. University of Warwick; Reino Unido
Fil: Brighton, Paul J.. University of Warwick; Reino Unido
Fil: Rawlings, Thomas M.. University of Warwick; Reino Unido
Fil: Muter, Joanne. University of Warwick; Reino Unido
Fil: Gori, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Lucas, Emma S.. University of Warwick; Reino Unido. University Of Sheffield. Faculty Of Medicine, Dentistry And Health, School Of Medicine;
Fil: Brosens, Jan J.. University Hospitals Coventry and Warwickshire NHS Trust; Reino Unido. University of Warwick; Reino Unido
Fil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
HSPA5
DECIDUALIZATION
SENESCENCE
ER STRESS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/268007
Acceder
id CONICETDig_a7285a1d5a12ae7c75a0a4b2ef11a342
oai_identifier_str oai:ri.conicet.gov.ar:11336/268007
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cellsFernández, Laura del CarmenKong, Chow SengAlkhoury, MajdTryfonos, MariaBrighton, Paul J.Rawlings, Thomas M.Muter, JoanneGori, María SoledadPerez Leiros, ClaudiaLucas, Emma S.Brosens, Jan J.Ramhorst, Rosanna ElizabethHSPA5DECIDUALIZATIONSENESCENCEER STRESShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Decidualization denotes the process of inflammatory reprogramming of endometrial stromal cells (EnSC) into specialized decidual cells (DC). During this process, EnSC are subjected to endoplasmic reticulum (ER) stress as well as acute cellular senescence. Both processes contribute to the proinflammatory mid-luteal implantation window and their dysregulation has been implicated in reproductive failure. Here, we evaluated the link between ER stress, decidual differentiation and senescence. In-silico analysis identified HSPA5 gene, codifying the ER chaperone BiP, as a potentially critical regulator of cell fate divergence of decidualizing EnSC into anti-inflammatory DC and pro-inflammatory senescent decidual cells (snDC). Knockdown of HSPA5 in primary EnSC resulted both in decreased expression of DC marker genes and attenuated induction of senescence associated β-galactosidase activity, a marker of snDC. Stalling of the decidual reaction upon HSPA5 knockdown was apparent at 8 days of differentiation and was preceded by the upregulation of ER stress associated proteins IRE1α and PERK. Further, HSPA5 knockdown impaired colony-forming unit activity of primary EnSC, indicative of loss of cellular plasticity. Together, our results point to a key role for HSPA5/BiP in decidual transformation of EnSCs and highlight the importance of constraining ER stress levels during this process.Fil: Fernández, Laura del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. University of Warwick; Reino UnidoFil: Kong, Chow Seng. University of Warwick; Reino UnidoFil: Alkhoury, Majd. University Hospitals Coventry and Warwickshire NHS Trust; Reino UnidoFil: Tryfonos, Maria. University of Warwick; Reino UnidoFil: Brighton, Paul J.. University of Warwick; Reino UnidoFil: Rawlings, Thomas M.. University of Warwick; Reino UnidoFil: Muter, Joanne. University of Warwick; Reino UnidoFil: Gori, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Lucas, Emma S.. University of Warwick; Reino Unido. University Of Sheffield. Faculty Of Medicine, Dentistry And Health, School Of Medicine;Fil: Brosens, Jan J.. University Hospitals Coventry and Warwickshire NHS Trust; Reino Unido. University of Warwick; Reino UnidoFil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaNature2024-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/268007Fernández, Laura del Carmen; Kong, Chow Seng; Alkhoury, Majd; Tryfonos, Maria; Brighton, Paul J.; et al.; The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells; Nature; Scientific Reports; 14; 1; 10-2024; 1-122045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-024-76241-zinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-024-76241-zinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:26Zoai:ri.conicet.gov.ar:11336/268007instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:11:27.241CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
title The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
spellingShingle The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
Fernández, Laura del Carmen
HSPA5
DECIDUALIZATION
SENESCENCE
ER STRESS
title_short The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
title_full The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
title_fullStr The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
title_full_unstemmed The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
title_sort The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
dc.creator.none.fl_str_mv Fernández, Laura del Carmen
Kong, Chow Seng
Alkhoury, Majd
Tryfonos, Maria
Brighton, Paul J.
Rawlings, Thomas M.
Muter, Joanne
Gori, María Soledad
Perez Leiros, Claudia
Lucas, Emma S.
Brosens, Jan J.
Ramhorst, Rosanna Elizabeth
author Fernández, Laura del Carmen
author_facet Fernández, Laura del Carmen
Kong, Chow Seng
Alkhoury, Majd
Tryfonos, Maria
Brighton, Paul J.
Rawlings, Thomas M.
Muter, Joanne
Gori, María Soledad
Perez Leiros, Claudia
Lucas, Emma S.
Brosens, Jan J.
Ramhorst, Rosanna Elizabeth
author_role author
author2 Kong, Chow Seng
Alkhoury, Majd
Tryfonos, Maria
Brighton, Paul J.
Rawlings, Thomas M.
Muter, Joanne
Gori, María Soledad
Perez Leiros, Claudia
Lucas, Emma S.
Brosens, Jan J.
Ramhorst, Rosanna Elizabeth
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HSPA5
DECIDUALIZATION
SENESCENCE
ER STRESS
topic HSPA5
DECIDUALIZATION
SENESCENCE
ER STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Decidualization denotes the process of inflammatory reprogramming of endometrial stromal cells (EnSC) into specialized decidual cells (DC). During this process, EnSC are subjected to endoplasmic reticulum (ER) stress as well as acute cellular senescence. Both processes contribute to the proinflammatory mid-luteal implantation window and their dysregulation has been implicated in reproductive failure. Here, we evaluated the link between ER stress, decidual differentiation and senescence. In-silico analysis identified HSPA5 gene, codifying the ER chaperone BiP, as a potentially critical regulator of cell fate divergence of decidualizing EnSC into anti-inflammatory DC and pro-inflammatory senescent decidual cells (snDC). Knockdown of HSPA5 in primary EnSC resulted both in decreased expression of DC marker genes and attenuated induction of senescence associated β-galactosidase activity, a marker of snDC. Stalling of the decidual reaction upon HSPA5 knockdown was apparent at 8 days of differentiation and was preceded by the upregulation of ER stress associated proteins IRE1α and PERK. Further, HSPA5 knockdown impaired colony-forming unit activity of primary EnSC, indicative of loss of cellular plasticity. Together, our results point to a key role for HSPA5/BiP in decidual transformation of EnSCs and highlight the importance of constraining ER stress levels during this process.
Fil: Fernández, Laura del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. University of Warwick; Reino Unido
Fil: Kong, Chow Seng. University of Warwick; Reino Unido
Fil: Alkhoury, Majd. University Hospitals Coventry and Warwickshire NHS Trust; Reino Unido
Fil: Tryfonos, Maria. University of Warwick; Reino Unido
Fil: Brighton, Paul J.. University of Warwick; Reino Unido
Fil: Rawlings, Thomas M.. University of Warwick; Reino Unido
Fil: Muter, Joanne. University of Warwick; Reino Unido
Fil: Gori, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Lucas, Emma S.. University of Warwick; Reino Unido. University Of Sheffield. Faculty Of Medicine, Dentistry And Health, School Of Medicine;
Fil: Brosens, Jan J.. University Hospitals Coventry and Warwickshire NHS Trust; Reino Unido. University of Warwick; Reino Unido
Fil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description Decidualization denotes the process of inflammatory reprogramming of endometrial stromal cells (EnSC) into specialized decidual cells (DC). During this process, EnSC are subjected to endoplasmic reticulum (ER) stress as well as acute cellular senescence. Both processes contribute to the proinflammatory mid-luteal implantation window and their dysregulation has been implicated in reproductive failure. Here, we evaluated the link between ER stress, decidual differentiation and senescence. In-silico analysis identified HSPA5 gene, codifying the ER chaperone BiP, as a potentially critical regulator of cell fate divergence of decidualizing EnSC into anti-inflammatory DC and pro-inflammatory senescent decidual cells (snDC). Knockdown of HSPA5 in primary EnSC resulted both in decreased expression of DC marker genes and attenuated induction of senescence associated β-galactosidase activity, a marker of snDC. Stalling of the decidual reaction upon HSPA5 knockdown was apparent at 8 days of differentiation and was preceded by the upregulation of ER stress associated proteins IRE1α and PERK. Further, HSPA5 knockdown impaired colony-forming unit activity of primary EnSC, indicative of loss of cellular plasticity. Together, our results point to a key role for HSPA5/BiP in decidual transformation of EnSCs and highlight the importance of constraining ER stress levels during this process.
publishDate 2024
dc.date.none.fl_str_mv 2024-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/268007
Fernández, Laura del Carmen; Kong, Chow Seng; Alkhoury, Majd; Tryfonos, Maria; Brighton, Paul J.; et al.; The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells; Nature; Scientific Reports; 14; 1; 10-2024; 1-12
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/268007
identifier_str_mv Fernández, Laura del Carmen; Kong, Chow Seng; Alkhoury, Majd; Tryfonos, Maria; Brighton, Paul J.; et al.; The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells; Nature; Scientific Reports; 14; 1; 10-2024; 1-12
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-024-76241-z
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-024-76241-z
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842270158473658368
score 13.13397

Publicaciones similares