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Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model [RNA-Seq]

ABSTRACT: Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model [RNA-Seq]

PROVIDER: PRJNA1020785 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26162379_1.fastq.gz	Fastqsanger.gz
	SRR26162379_2.fastq.gz	Fastqsanger.gz
	SRR26162380_1.fastq.gz	Fastqsanger.gz
	SRR26162380_2.fastq.gz	Fastqsanger.gz
	SRR26162381_1.fastq.gz	Fastqsanger.gz

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Project description:BackgroundHypertrophic scars cause impaired skin appearance and function, seriously affecting physical and mental health. Due to medical ethics and clinical accessibility, the collection of human scar specimens is frequently restricted, and the establishment of scar experimental animal models for scientific research is urgently needed. The four most commonly used animal models of hypertrophic scars have the following drawbacks: the rabbit ear model takes a long time to construct; the immunodeficient mouse hypertrophic scar model necessitates careful feeding and experimental operations; female Duroc pigs are expensive to purchase and maintain, and their large size makes it difficult to produce a significant number of models; and mouse scar models that rely on tension require special skin stretch devices, which are often damaged and shed, resulting in unstable model establishment. Our group overcame the shortcomings of previous scar animal models and created a new mouse model of hypertrophic scarring induced by suture anchoring at the wound edge.MethodsWe utilized suture anchoring of incisional wounds to impose directional tension throughout the healing process, restrain wound contraction, and generate granulation tissue, thus inducing scar formation. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage and the wound edges on the lower back relaxed as a control. Macroscopic manifestation, microscopic histological analysis, mRNA sequencing, bioinformatics, and in vitro cell assays were also conducted to verify the reliability of this method.ResultsCompared with those in relaxed controls, the fibrotic changes in stretched wounds were more profound. Histologically, the stretched scars were hypercellular, hypervascular, and hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. In addition, the stretched scars exhibited transcriptional overlap with mechanically stretched scars, and human hypertrophic and keloid scars. Phosphatidylinositol 3-kinase-serine/threonine-protein kinase B signaling was implicated as a profibrotic mediator of apoptosis resistance under suture-induced tension.ConclusionsThis straightforward murine model successfully induces cardinal molecular and histological features of pathological hypertrophic scarring through localized suture tension to inhibit wound contraction. The model enables us to interrogate the mechanisms of tension-induced fibrosis and evaluate anti-scarring therapies.

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Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model [RNA-Seq]

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