Skin scarring.
Ontology highlight
ABSTRACT:
SUBMITTER: Bayat A
PROVIDER: S-EPMC1125033 | biostudies-literature | 2003 Jan
REPOSITORIES: biostudies-literature
Publications
Skin scarring.
Bayat A A McGrouther D A DA Ferguson M W J MW
BMJ (Clinical research ed.) 20030101 7380
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Project description:The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.
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Project description:Although skin scarring is considered by some to be a minor, unavoidable consequence in response to skin injury, for many patients, cosmetically unsightly scars may cause uncomfortable symptoms and loss of function plus significant psycho-social distress. Despite their high prevalence and commonality, defining skin scars and their optimal management has proven problematic. Therefore, a literature search to assess the current evidence-base for scarring treatment options was conducted, and only those deemed Levels of Evidence 1 or 2 were included. Understanding the spectrum of skin scarring in the first instance is imperative, and is mainly comprised of four distinct endotypes; Stretched (flat), Contracted, Atrophic, and Raised for which the acronym S.C.A.R. may be used. Traditionally, scar assessment and response to therapy has employed the use of subjective scar scales, although these are now being superseded by non-invasive, objective and quantitative measurement devices. Treatment options will vary depending on the specific scar endotype, but fall under one of 3 main categories: (1) Leave alone, (2) Non-invasive, (3) Invasive management. Non-invasive (mostly topical) management of skin scarring remains the most accessible, as many formulations are over-the-counter, and include silicone-based, onion extract-based, and green tea-based, however out of the 52 studies identified, only 28 had statistically significant positive outcomes. Invasive treatment options includes intralesional injections with steroids, 5-FU, PDT, and laser with surgical scar excision as a last resort especially in keloid scar management unless combined with an appropriate adjuvant therapy. In summary, scar management is a rapidly changing field with an unmet need to date for a structured and validated approach.
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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:During wound healing, excessive inflammation, angiogenesis, and differentiated human dermal fibroblast (HDF ) function contribute to scarring, whereas hyperpigmentation negatively affects scar quality. Over 100 million patients heal with a scar every year. To investigate the role of the beta 2 adrenergic receptor (β2AR) in wound scarring, the ability of beta 2 adrenergic receptor agonist (β2ARag) to alter HDF differentiation and function, wound inflammation, angiogenesis, and wound scarring was explored in HDFs, zebrafish, chick chorioallantoic membrane assay (CAM), and a porcine skin wound model, respectively. Here we identify a β2AR-mediated mechanism for scar reduction. β2ARag significantly reduced HDF differentiation, via multiple cAMP and/or fibroblast growth factor 2 or basic FGF (FGF2)-dependent mechanisms, in the presence of transforming growth factor betaβ1, reduced contractile function, and inhibited mRNA expression of a number of profibrotic markers. β2ARag also reduced inflammation and angiogenesis in zebrafish and CAMs in vivo, respectively. In Red Duroc pig full-thickness wounds, β2ARag reduced both scar area and hyperpigmentation by almost 50% and significantly improved scar quality. Indeed, mechanisms delineated in vitro and in other in vivo models were evident in the β2ARag-treated porcine scars in vivo. Both macrophage infiltration and angiogenesis were initially decreased, whereas DF function was impaired in the β2ARag-treated porcine wound bed. These data collectively reveal the potential of β2ARag to improve skin scarring.
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Project description:Hypertrophic scars can cause pain, movement restrictions, and reduction in the quality of life. Despite numerous options to treat hypertrophic scarring, efficient therapies are still scarce, and cellular mechanisms are not well understood. Factors secreted by peripheral blood mononuclear cells (PBMCsec) have been previously described for their beneficial effects on tissue regeneration. In this study, we investigated the effects of PBMCsec on skin scarring in mouse models and human scar explant cultures at single-cell resolution (scRNAseq). Mouse wounds and scars, and human mature scars were treated with PBMCsec intradermally and topically. The topical and intradermal application of PBMCsec regulated the expression of various genes involved in pro-fibrotic processes and tissue remodeling. We identified elastin as a common linchpin of anti-fibrotic action in both mouse and human scars. In vitro, we found that PBMCsec prevents TGFβ-mediated myofibroblast differentiation and attenuates abundant elastin expression with non-canonical signaling inhibition. Furthermore, the TGFβ-induced breakdown of elastic fibers was strongly inhibited by the addition of PBMCsec. In conclusion, we conducted an extensive study with multiple experimental approaches and ample scRNAseq data demonstrating the anti-fibrotic effect of PBMCsec on cutaneous scars in mouse and human experimental settings. These findings point at PBMCsec as a novel therapeutic option to treat skin scarring.
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Project description:Mast cells (MCs) are an important immune cell type in the skin and play an active role during wound healing. MCs produce mediators that can enhance acute inflammation, stimulate re-epithelialisation as well as angiogenesis, and promote skin scarring. There is also a link between MCs and abnormal pathological cutaneous scarring, with increased numbers of MCs found in hypertrophic scars and keloid disease. However, there has been conflicting data regarding the specific role of MCs in scar formation in both animal and human studies. Whilst animal studies have proved to be valuable in studying the MC phenomenon in wound healing, the appropriate translation of these findings to cutaneous wound healing and scar formation in human subjects remains crucial to elucidate the role of these cells and target treatment effectively. Therefore, this perspective paper will focus on evaluation of the current evidence for the role of MCs in skin scarring in both animals and humans in order to identify common themes and future areas for translational research.
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Project description:Acne scars are the reason for significant morbidity among dermatology outpatients. With more modalities being introduced every year, it is important to choose the best one suited for a particular type of scar for each patient to obtain an optimum result. Guidelines on acne scar management in the skin of color are not available where the therapeutic effect and side effect profile of the modalities can vary significantly. This narrative review looked at critical evaluation of the available modalities to find the level of evidence and therapeutic ladder of management of different types of acne scars. Treatment options for different types of scars have been described. Evidence level for each type of modality for the individual type of scar was calculated using the Strength of Recommendation Taxonomy (SORT) developed by editors of the US family medicine and primary care journals. In addition, various newer and emerging treatment options, such as dermal cell suspension, jet volumetric remodeling, and radiofrequency subcision, have been discussed. The highest level of evidence is available for microneedling, fractional radiofrequency, fractional CO2, and erbium:yttrium aluminum garnet laser for mild to moderate grade scars. Trichloroacetic acid chemical reconstruction of skin scars showed efficacy in ice pick scars. Grade 4 scars improve poorly with resurfacing procedures, where punch excision and punch elevation can be tried. Platelet-rich plasma therapy was effective in combination with lasers and microneedling. Overall there is lack of high-quality data in the management of post acne scars. Combination treatment has shown better efficacy compared to single modalities.
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Project description:BACKGROUND:Pathological scarring in wounds is a prevalent clinical outcome with limited prognostic options. The objective of this study was to investigate whether cellular signaling proteins could be used as prognostic biomarkers of pathological scarring in traumatic skin wounds. METHODS:We used our previously developed and validated computational model of injury-initiated wound healing to simulate the time courses for platelets, 6 cell types, and 21 proteins involved in the inflammatory and proliferative phases of wound healing. Next, we analysed thousands of simulated wound-healing scenarios to identify those that resulted in pathological (i.e., excessive) scarring. Then, we identified candidate proteins that were elevated (or decreased) at the early stages of wound healing in those simulations and could therefore serve as predictive biomarkers of pathological scarring outcomes. Finally, we performed logistic regression analysis and calculated the area under the receiver operating characteristic curve to quantitatively assess the predictive accuracy of the model-identified putative biomarkers. RESULTS:We identified three proteins (interleukin-10, tissue inhibitor of matrix metalloproteinase-1, and fibronectin) whose levels were elevated in pathological scars as early as 2 weeks post-wounding and could predict a pathological scarring outcome occurring 40 days after wounding with 80% accuracy. CONCLUSION:Our method for predicting putative prognostic wound-outcome biomarkers may serve as an effective means to guide the identification of proteins predictive of pathological scarring.
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Project description:Mammals heal faster with imperfect fibrotic scars, while amphibians regenerate slower with scarless wound healing. These observations support the prevailing paradigm that speed of wound closure is inversely related to repair quality. Here we find evidence that this is a false trade-off. In multiple injury models, mice lacking CXCR2 (CXCR2-KO) globally improved both speed and quality of skin wound healing, including hair regeneration. We found CXCR2 primarily expressed in neutrophils, and injury induced neutrophils to secrete neutrophil extracellular traps (NETs). Mice engineered to be specifically deficient in myeloid CXCR2 or NET production partially recreated the phenotype with improved early speed of wound closure. Thus, CXCR2+ neutrophils regulate the speed of wound closure.
2024-10-03 | GSE245864 | GEO
Project description:BackgroundTransplantation of mesenchymal stem cells (MSC) has been proposed to improve wound healing. However, as these cells only transiently survive in the implantation site, the mechanisms underlying this beneficial healing response are associated with restorative paracrine effects of MSC matricellular factors on resident stromal cells. However, this requires that the recipient has a robust reservoir of viable cells. Here, we examine the influence of MSCs on the behavior of cotransplanted fibroblasts, in a manner to provide augmented cellular reserve to debilitated individuals, specifically focusing on matrix remodeling following in-vivo wounding.MethodsUsing a Hylan-A dermal filler hydrogel containing collagen I and tenascin-C for delivery and increased survival of transplanted cells, we find that cotransplantation of MSCs with fibroblasts reduces scarring.ResultsTransplanted xenogeneic MSCs augmented fibroblast proliferation, migration, and extracellular matrix deposition critical for wound closure, and reduced inflammation following wounding. MSCs also corrected matrix remodeling by CXCR3-deficient fibroblasts which otherwise led to hypertrophic scarring. This effect was superior to MSC or fibroblast transplantation alone.ConclusionsTaken together, these data suggest that MSCs, even if eventually rejected, transplanted with fibroblasts normalize matrix regeneration during healing. The current study provides insight into cellular therapies as a viable method for antifibrotic treatment and demonstrates that even transiently engrafted cells can have a long-term impact via matrix modulation and education of other tissue cells.
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