Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
27 Sep 2024
Historique:
received: 31 01 2023
accepted: 03 09 2024
medline: 28 9 2024
pubmed: 28 9 2024
entrez: 27 9 2024
Statut: epublish

Résumé

Scar tissue formation is a hallmark of wound repair in adults and can chronically affect tissue architecture and function. To understand the general phenomena, we sought to explore scar-driven imbalance in tissue homeostasis caused by a common, and standardized surgical procedure, the uterine scar due to cesarean surgery. Deep uterine scar is associated with a rapidly increasing condition in pregnant women, placenta accreta spectrum (PAS), characterized by aggressive trophoblast invasion into the uterus, frequently necessitating hysterectomy at parturition. We created a model of uterine scar, recapitulating PAS-like invasive phenotype, showing that scar matrix activates mechanosensitive ion channel, Piezo1, through glycolysis-fueled cellular contraction. Piezo1 activation increases intracellular calcium activity and Protein kinase C activation, leading to NF-κB nuclear translocation, and MafG stabilization. This inflammatory transformation of decidua leads to production of IL-8 and G-CSF, chemotactically recruiting invading trophoblasts towards scar, initiating PAS. Our study demonstrates aberrant mechanics of scar disturbs stroma-epithelia homeostasis in placentation, with implications in cancer dissemination.

Identifiants

pubmed: 39333481
doi: 10.1038/s41467-024-52351-0
pii: 10.1038/s41467-024-52351-0
doi:

Substances chimiques

Ion Channels 0
PIEZO1 protein, human 0
NF-kappa B 0
Protein Kinase C EC 2.7.11.13
Interleukin-8 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8379

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ID : 1R01HD112424
Organisme : U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ID : 1K99HD105973
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : 5R37CA248161

Informations de copyright

© 2024. The Author(s).

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Auteurs

Du Wenqiang (D)

Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, USA.
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA.

Ashkan Novin (A)

Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, USA.
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA.

Yamin Liu (Y)

Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA.

Junaid Afzal (J)

Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Yasir Suhail (Y)

Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, USA.
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA.

Shaofei Liu (S)

Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, USA.
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA.

Nicole R Gavin (NR)

Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT, USA.

Jennifer R Jorgensen (JR)

Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT, USA.

Christopher M Morosky (CM)

Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT, USA.

Reinaldo Figueroa (R)

Department of Obstetrics and Gynecology, Saint Francis Hospital and Medical Center, Hartford, CT, USA.

Tannin A Schmidt (TA)

Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, USA.

Melinda Sanders (M)

Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT, USA.
Department of Pathology, University of Connecticut Health Center, Farmington, CT, USA.

Molly A Brewer (MA)

Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT, USA.
Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, USA. kshitiz@uchc.edu.
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA. kshitiz@uchc.edu.

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