Journal of Investigative Dermatology RSS feed.
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3D culture067, 083, 285, 311, 315, 410, 451, 460, 529, 536, 542, 561, 677, 710, 743, 825, 883, 896, 909, 918
Rhomboid family protein RHBDF2 plays an important role in wound healing. A gain-of-function mutation in the Rhbdf2 genetriggers accelerated ear wound closure in curly bare (Rhbdf2cub/cub) mice byenhancing cell proliferation and migration through enhanced amphiregulin (AREG) production. To determine early-stage networks and biological processes that are alteredbetween Rhbdf2+/+ and Rhbdf2cub/cub mice after wounding, we performed transcriptome analysis at 0h, 15m, 2h, and 24h post-wounding. Increased baseline expression of genes acting within the extracellular signal–regulated kinase ERK1/2 pathway (0h) and the nuclear factor kappa B (NFkB) pathway (15 m), were followed by gene alterations associated with collagen synthesis (2h) and histone modification (24h).
After injury, skin rapidly repairs damage through robust and redundant cellular interactions that reseal the epidermal barrier and repopulate the dermis. Fibroblasts represent the most abundant mesenchymal cell type within wound beds and are responsible for extracellular matrix (ECM) deposition. While heterogeneity exists among dermal fibroblast populations, little is known about how specific subsets are activated and functionally contribute to skin repair. Here, we show heterogeneity among wound bed fibroblasts based on the presence of fibroblast-associated cell surface markers CD9, CD26, CD29, CD34, Sca1 and PDGFRa and find the most abundant population of fibroblasts is labeled by adipocyte precursor cell markers CD29, CD34 and Sca1.
Chronic wounds represent a major and rising health and economic burden worldwide. There is a continued search towards more effective wound therapy. We found significantly reduced microRNA-132 (miR-132) expression in human diabetic ulcers compared to normal skin wounds, and also in skin wounds of leptin receptor-deficient (db/db) diabetic mice compared to wild-type mice. Local replenishment of miR-132 in the wounds of db/db mice accelerated wound closure effectively, which was accompanied by increased proliferation of wound-edge keratinocytes and reduced inflammation.
Venous leg ulcers (VLUs) are the most prevalent type of leg ulcer in the US. Better understanding of factors associated with healing is needed. We performed a secondary analysis of 3 phase 3 multi-center trials that studied a novel cell therapy for refractory VLU, which was ineffective. Patients with non-healing VLUs that failed to improve with standard compression were studied. The trials endpont was closure by 12 weeks. We focused on evaluating the relationship between various systemic medications and VLU healing.
Regeneration via the lineage reprogramming of one cell lineage to another is believed to occur only in fish and amphibians, but it is not observed in mammals. We discovered in mouse that during wound healing adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and non-adipogenic. The transcription factors, Zfp423 and Pparg, normally expressed during adipocyte development, were reactivated and were required for adipogenic reprogramming of myofibroblasts. Myofibroblast reprogramming required the presence of neogenic hair follicles, which triggered Bone Morphogenic Protein (BMP) signaling and subsequent Zfp423 activation.
Over 80 million acute wounds occur every year and the vast majority result in scar formation. However, this process often fails in wounds that are too large to heal resulting in complications such as infection. While natural derived tissue scaffolds can accelerate wound healing, they are often cost prohibitive until a wound becomes chronic. To this end, we created a flowable microporous annealed particle (MAP) hydrogel scaffold that crosslinks in situ to itself and to the wound bed enzymatically using MMP-degradable peptides to accelerate wound healing (http://dx.doi.org/10.1038/nmat4294).
Chronic non-healing wounds, commonly found in diabetic patients, affect more than 5 million people in the United States every year. However, even with best standard of care, less than 50% of these wounds heal. Evidence suggests that inflammation contributes to wound chronicity. Recent advances have shown a role for serotonin (5-HT) and the selective serotonin reuptake inhibitor (SSRI) fluoxetine in immune modulation. Using a diabetic mouse model of impaired wound healing, we demonstrated that a novel topical formulation of fluoxetine improved wound healing in vivo by targeting inflammation and increasing both re-epithelialization and angiogenesis.
Chronic wounds are major health care problem, accounting for 2-3% of the total health budget. Pre-clinical and clinical trials with Mesenchymal Stem Cell (MSC)-based therapy suggest this is a promising treatment option, due to the beneficial effects of immunomodulation and the paracrine effects. We are developing bioengineered wound scaffolds containing hypoxia-treated, allogeneic human MSCs and a beta-adrenergic antagonist, timolol (Tim), to treat splinted wounds on the dorsum of db/db mice. Outcome is wound epithelialization, measured histo-morphometrically using H&E or keratin 5 staining.
Although diverse immunomodulatory effects of vitamin D are increasingly being recognized, the ability of oral vitamin D to rapidly modulate immune responses in vivo has not been established in humans. We designed an interventional study to test the hypothesis that oral vitamin D would be capable of rapidly attenuating experimental sunburn. Twenty healthy adults were randomized, in a double-blinded fashion, to receive either placebo or a high dose of vitamin D3 (cholecalciferol) one hour after experimental sunburn induced by an erythemogenic dose of simulated solar radiation.
Chronic wounds often require long treatment time to heal. Little is known about patients’ expectations concerning the time it would take for their wound to heal and what factors might affect their prediction. Subjects with one target ulcer (1-25cm2) were recruited from our clinic. Patients were asked to predict their wound healing time, while their charts were subsequently reviewed to retrieve time to healing. Wound-specific data including etiology, surface area, and number of prior episodes were recorded.
Ca2+ fluxes direct keratinocyte differentiation, cell-to-cell adhesion, migration, epidermal barrier homeostasis, and wound healing processes. We previously demonstrated that barrier perturbation causes calcium mobilization from intracellular stores, which result in a sudden and transient elevation of cytosolic calcium levels in all epidermal layers. To further investigate the spatial and temporal dynamics of calcium signaling in living epidermis, with interest to signal transduction from the outer to inner epidermis, we used 2-photon excitation microscopy to visualize calcium fluctuations in the epidermis of K14creGCaMP3 mice, an approach that allows detection of fast dynamics.
Alkylating agents such as nitrogen mustard (NM) are known to cause severe blistering and systemic toxicity upon exposure. Our previous work demonstrated the efficacy of a single dose of 25-hydroxyvitamin D3 (25(OH)D) required to improve local skin wound healing and recover animals from pancytopenia and death primarily through suppression of activated macrophages populating the bone marrow (BM). In this study we propose to explore if 25(OH)D promotes recovery by expanding a specific subset of anti-inflammatory macrophages.
Introduction: Hypertrophic scars from burn injuries are painful and disfiguring. Dysregulated fibrogenesis plays a significant role in their formation. The discovery of an agent that can mitigate fibrosis would be tremendously beneficial in treating hypertrophic scars. Rose Bengal (RB) is a photoactive dye, demonstrated to aid in wound healing with minimal scarring. RB has not been studied on fibroblasts from hypertrophic scars. Objective: To investigate the effects of Rose Bengal on cell viability and functions in fibroblasts from hypertrophic scars.
Cutaneous inflammation from UV exposure causes epidermal damage, cellular infiltration and secretion of pro-inflammatory mediators that exacerbate tissue destruction. Recovery is mediated chiefly by anti-inflammatory (M2) macrophages that suppress inflammation and augments epidermal regeneration. Previously we demonstrated in both a murine model of UV–induced cutaneous inflammation and a human interventional study, that a single administration of 25(OH)D (VitD) or a single dose of oral cholecalciferol 1h following UV exposure, was sufficient to diminish skin inflammation and arrest tissue damage.
Laminin alpha5 is a major component of the skin basement membrane underneath the basal layer keratinocytes of epidermis. The alpha chain of laminins has been shown to contain the primary binding sites for cell surface receptors that mediate cell attachment and migration which are two dynamic key events for keratinocytes during wound re-epithelialization. In this study we first evaluated the role of laminin alpha5 in cell attachment and migration in normal human skin keratinocytes using gene knockdown strategy with RNA interference.