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

ABSTRACT: Hypertrophic scars arise from dysregulated wound healing under prolonged mechanical tension, causing disfiguring fibrosis. However, limited preclinical models replicate key features of human tension-induced scarring. We developed an innovative murine model utilizing suture anchoring to impose persistent transverse-axial stretch across healing incisions, mimicking excessive wound tension that leads to hypertrophy clinically. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage while leaving wound edges on the lower back relaxed. This localized anchoring restrained wound contraction, maintaining high tension throughout remodeling analogous to scars widening under stress. Stretched upper wounds developed profound fibrotic changes compared to relaxed controls. Scars induced by suture-anchored tension displayed macroscopic hypertrophy, hardness, erythema, and pruritis up to 3 months. Histologically, scars induced by suture-anchored tension were hypercellular, hypervascular, hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. MiRNA sequencing revealed the different signature in suture-anchored tension induced hypertrophic scars compared to control normal scars.

ORGANISM(S): Mus musculus

PROVIDER: GSE243948 | GEO | 2023/09/28

REPOSITORIES: GEO

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

Project description:Hypertrophic scars arise from dysregulated wound healing under prolonged mechanical tension, causing disfiguring fibrosis. However, limited preclinical models replicate key features of human tension-induced scarring. We developed an innovative murine model utilizing suture anchoring to impose persistent transverse-axial stretch across healing incisions, mimicking excessive wound tension that leads to hypertrophy clinically. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage while leaving wound edges on the lower back relaxed. This localized anchoring restrained wound contraction, maintaining high tension throughout remodeling analogous to scars widening under stress. Stretched upper wounds developed profound fibrotic changes compared to relaxed controls. Scars induced by suture-anchored tension displayed macroscopic hypertrophy, hardness, erythema, and pruritis up to 3 months. Histologically, scars induced by suture-anchored tension were hypercellular, hypervascular, hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. MRNA sequencing revealed the fibrogenic signature in suture-anchored tension induced hypertrophic scars, which exhibited transcriptional overlap with mechanically-stretched scars, human hypertrophic and keloid scars.

2023-09-28 | GSE243949 | GEO

Long noncoding RNA (lncRNA) expression profiles of hypertrophic scar fibroblasts treated with glucocorticoids under mechanical stretch environment

Project description:After disruption of the skin, fibroblasts along wound edges are constantly exposed to high levels of stress, resulting in increased collagen synthesis and decreased apoptosis. Emerge evidences shows that, the hypertrophic scars tissue fibrosis phenomena are original from the intrinsic cellular mechanical stretch. Traditional glucocorticoids on hypertrophic scarring have been performed for 30 years, utilizing for their anti-inflammatory, anti-allergenic and immunomodulatory effects and for their well-established, pro-apoptotic effects on hematological malignancies. To explore effects of glucocorticoid triamcinolone acetonide (TA) for responses to mechanical stress in hypertrophic scars fibroblasts (HSFB), we performed microarrays to explore long noncoding RNA expression.

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Project description:After disruption of the skin, fibroblasts along wound edges are constantly exposed to high levels of stress, resulting in increased collagen synthesis and decreased apoptosis. Emerge evidences shows that, the hypertrophic scars tissue fibrosis phenomena are original from the intrinsic cellular mechanical stretch. Traditional glucocorticoids on hypertrophic scarring have been performed for 30 years, utilizing for their anti-inflammatory, anti-allergenic and immunomodulatory effects and for their well-established, pro-apoptotic effects on hematological malignancies. To explore effects of glucocorticoid triamcinolone acetonide for responses to mechanical stress in hypertrophic scars fibroblasts (HSFB), we performed microarrays to explore the differential gene expression.

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The Role of the Mammalian Target of Rapamycin in Keloid and Hypertrophic Scars

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Expression data from the dermis of human stretched scars and patient-matched healthy dermis from occipital scalps

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High-salt diet promotes hypertrophic scarring through TRPC3-mediated mitochondrial Ca2+ homeostasis dysfunction

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Real-time quantitative PCR analysis of murine non-ischemic and ischemic wound edge

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Single cell sequencing identifies serine proteases as regulators of myofibroblast differentiation

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