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

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

PROVIDER: PRJNA1123298 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29382646_1.fastq.gz	Fastqsanger.gz
	SRR29382646_2.fastq.gz	Fastqsanger.gz
	SRR29382647_1.fastq.gz	Fastqsanger.gz
	SRR29382647_2.fastq.gz	Fastqsanger.gz
	SRR29382648_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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