Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model
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ABSTRACT:
PROVIDER: PRJNA1020782 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26161364.fastq.gz | Fastqsanger.gz | |||
| SRR26161365.fastq.gz | Fastqsanger.gz | |||
| SRR26161366.fastq.gz | Fastqsanger.gz | |||
| SRR26161367.fastq.gz | Fastqsanger.gz | |||
| SRR26161368.fastq.gz | Fastqsanger.gz |
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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. MiRNA sequencing revealed the different signature in suture-anchored tension induced hypertrophic scars compared to control normal scars.
2023-09-28 | GSE243948 | GEO
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
Project description:Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model [miRNA]
| PRJNA1020784 | ENA
Project description:Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model [RNA-Seq]
| PRJNA1020785 | ENA
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.
| S-EPMC11491161 | biostudies-literature
Project description:Hypertrophic skin scarring following dermal injury causes extreme pain and psychological trauma for patients. Unfortuately, we do not have effective treatments to prevent or reverse skin scarring. Using RNA and ATAC sequencing of mouse and human fibroblasts, we show that JUN expressing fibroblasts are responsible for skin scarring by regulating CD36 expression. In summary, we show that CD36 antagonism by represent a therapeutic target to overcome JUN hypertrophic skin scarring.
2021-06-22 | GSE178562 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-09-28 | GSE243950 | GEO
Project description:JUN promotes hypertrophic skin scarring via CD36
| PRJNA739661 | ENA
Project description:Diet High in salt content have been associated with cardiovascular disease and chronic inflammation. We recently demonstrated that transient receptor potential canonical 3 (TRPC3) channels regulate myofibroblast transdifferentiation in hypertrophic scars. Here, we examined how high salt activation of TRPC3 participates in hypertrophic scarring during wound healing. In vitro, we confirmed that high salt increased the TRPC3 protein expression and the marker of myofibroblast alpha smooth muscle actin (α-SMA) in wild-type mice (WT) primary cultured dermal fibroblasts but not Trpc3-/- mice. Activation of TRPC3 by high salt elevated cytosolic Ca2+ influx and mitochondrial Ca2+ uptake in dermal fibroblasts in a TRPC3-dependent manner. High salt activation of TRPC3 enhanced mitochondrial respiratory dysfunction and excessive reactive oxygen species (ROS) production by inhibiting pyruvate dehydrogenase action, that activated ROS-triggered Ca2+ influx and the Rho kinase/MLC pathway in WT mice but not Trpc3-/- mice. In vivo, a persistent high-salt diet promoted myofibroblast transdifferentiation and collagen deposition in a TRPC3-dependent manner. Therefore, this study demonstrates that high salt enhances myofibroblast transdifferentiation and promotes hypertrophic scar formation through enhanced mitochondrial Ca2+ homeostasis, which activates the ROS-mediated pMLC/pMYPT1 pathway. TRPC3 deficiency antagonizes high salt diet-induced hypertrophic scarring. TRPC3 may be a novel target for hypertrophic scarring during wound healing.
2023-10-24 | PXD042087 | Pride
Project description:Hypertrophic scarring (HS) is characterized by excessive extracellular matrix deposition, matrix metalloprotein gene activation, and fibroblast invasive growth. However, the methylation level of hypertrophic scarring is poorly understood. Genome wide DNA methylation profiling of normal skin and hypertrophic scar. The Illumina Infinium Methylation EPIC BeadChip (850K) was used to obtain DNA methylation profiles across approximately 853,307 CpGs in liquid based scar samples. Samples included 6 normal skin, and 6 hypertrophic scar.
2023-04-20 | GSE229848 | GEO