The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells.
Humans
Female
Endoplasmic Reticulum Chaperone BiP
/ metabolism
Stromal Cells
/ metabolism
Decidua
/ metabolism
Heat-Shock Proteins
/ metabolism
Endoplasmic Reticulum Stress
Endometrium
/ metabolism
Cellular Senescence
Cell Differentiation
Cells, Cultured
Gene Knockdown Techniques
Adult
Endoplasmic Reticulum
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 10 2024
29 10 2024
Historique:
received:
11
06
2024
accepted:
11
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39472623
doi: 10.1038/s41598-024-76241-z
pii: 10.1038/s41598-024-76241-z
doi:
Substances chimiques
Endoplasmic Reticulum Chaperone BiP
0
HSPA5 protein, human
0
Heat-Shock Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25992Subventions
Organisme : Wellcome Trust Investigator Award
ID : 212233/Z/18/Z
Informations de copyright
© 2024. The Author(s).
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