Journal Of Investigative Dermatology

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954 MagneTEskin – Orientation matters

Wed, 2019-05-01 00:00
Wounds and scarring represent an immense socio-economic burden, and although autologous skin grafting is the current gold standard for wound repair, it comes at the cost of significant donor site morbidity. Thus, in the wound healing field there has been a decades-long effort to develop alternatives to conventional autologous skin, but so far, these efforts have resulted in limited clinical utility. We recently found that small-diameter (about 500 μm) cores of skin tissue, which we termed micro skin tissue columns (MSTCs), can be harvested with minimal donor site morbidity.

953 Spray on skin: Engineering polymers for wound healing

Wed, 2019-05-01 00:00
Due to the challenges of skin grafting and the need for more facile methods to promote wound healing, researchers have since turned to synthetic polymers in order to engineer a material that can aid in the healing process. Herein we have developed a reversible thermal gel (RTG) aimed at mimicking native skin and encouraging wound healing. This polymer is comprised of a biomimetic backbone shown through FT-IR to have a similar structure to collagen. This backbone was conjugated with PNIPAAm, a thermosensitive water-soluble homopolymer that allows for rapid phase transition from a solution state to a physical gel when exposed to body temperature.

952 Topical nicotinic receptor activation improves wound bacterial infection outcomes by suppressing TLR2-mediated inflammation in diabetic wounds

Wed, 2019-05-01 00:00
Chronic inflammation is frequently observed in diabetic wounds and can occur, in part, via excessive TLR2 activation or production. Consequently, this can delay physiologic wound healing responses and increase diabetic host susceptibility to bacterial infection. The cholinergic anti-inflammatory pathway can directly affect skin antibacterial and wound healing responses via nicotinic acetylcholine receptors (nAChRs). Specifically, epidermal α7 nAChR (CHRNA7) can modulate the host response to wounding and/or wound bacterial infection.

951 The wound healing effect of a novel synthetic retinoid, seletinoid G, on cultured keratinocytes and human skin equivalents

Wed, 2019-05-01 00:00
We previously designed a novel synthetic retinoid, seletinoid G, and demonstrated that seletinoid G as an anti-aging compound can increase the expression of extracellular matrix proteins (type I procollagen, tropoelastin, and fibrillin-1) in human skin in vivo. In addition to its anti-aging efficacy, however, other activities have not been studied. In this study, we investigated the wound healing effects of seletinoid G on human keratinocyte cell line (HaCaT) and skin equivalents. An automated time-lapse imaging technique was used to visualize real-time keratinocyte migration and in vitro wound healing effect of seletinoid G.

950 Autophagy is inhibited in keloid-derived fibroblasts

Wed, 2019-05-01 00:00
The mechanistic target of rapamycin protein (mTOR) is a serine/threonine kinase that involves in several crucial cellular processes. Simultaneously, mTOR is also a negative regulator of autophagy. Previous studies reported that mTOR signaling was activated in keloid lesions, and mTOR inhibitors exhibited anti-keloid activity both in vitro and an ex vivo model. However, whether the autophagy inhibition contributes to the pathogenesis of keloid remains unclear. In this study, we determined autophagy level in both keloid fibroblasts (KFs) and keloid tissues, and investigated the effects of mTOR-dependent and mTOR-independent autophagy inducers.

949 Single cell RNA-seq and single cell ATAC-seq analyses during a treatment for dystrophic epidermolysis bullosa

Wed, 2019-05-01 00:00
Dystrophic epidermolysis bullosa (DEB) is a one of the most severe form of EB caused by mutations in COL7A1 (coding type VII collagen). DEB patients, without functional type VII collagen, suffer from the repetitive blistering and have high risk of early-onset aggressive squamous cell carcinoma. Recently, we found that a fragment of HMGB1 activates an endogenous tissue regeneration mechanism and ameliorates the DEB related manifestations in a DEB model mouse. This HMGB1 treatment model in the DEB mouse serves as a unique opportunity to investigate on how the skin can lose the integrity by loss of a single protein and how the damaged skin can be reconstructed.

948 CD44 regulates α-SMA gene expression via a novel G-actin/MRTF mediated pathway that requires TGFβR/p38MAPK activity in murine skin fibroblasts

Wed, 2019-05-01 00:00
During skin wound healing, fibroblasts differentiate into myofibroblasts (MF) that assist in wound contraction and repair. Neoexpression of α-smooth muscle actin (α-SMA), an established marker for MF differentiation, is driven by TGFβ receptor (TGFβR)-mediated signaling. Hyaluronan (HA) and its receptor CD44 on cell surface can also participate in this process. To further understand how HA, CD44, and TGFβR pathways interact, primary mouse skin fibroblasts were isolated and treated in vitro with recombinant TGF-β1 (rTGF-β1) and the expression of α-SMA and CD44 were increased.

947 Accelerating wound healing mechanisms with cold atmospheric plasma

Wed, 2019-05-01 00:00
Chronic wounds impose significant morbidity and mortality on 1-2% of the global population. With limited treatment options, they remain a major area of unmet clinical need. Cold atmospheric plasma (partially ionized gas, CAP) represents novel technology capable of accelerating wound healing processes while simultaneously decontaminating skin of bacteria, including biofilms and multi-drug resistant bacteria. CAP operate at room temperature and generate bio-active chemicals such as nitric oxide (NO) as part of a gas effluent.

946 Therapeutic effect of combined platelet-rich plasma strategies on morphea

Wed, 2019-05-01 00:00
Platelet-rich plasma (PRP) therapy plays an important role in the tissue regeneration process which has been successfully used in the treatment of various dermatologic conditions. The aim of this pilot study was to assess the clinical benefit of combined PRP strategies including autologous PRP injection and a new developed method of platelet-rich plasma gel (PRPG) filling, which have synergic effects on skin elasticity, dermal remodeling and re-vascularization. Six patients who were diagnosed as plaque morphea and linear morphea under the confirmation of histopathology, and assessed by ultrasonography.

945 Topological transformation reveals a simplified 2-dimensional healing strategy to repair 3-dimensional injury in hair follicles

Wed, 2019-05-01 00:00
The structure of epithelial organs varies from 2- dimensional planar sheets to 3-dimentional folded architecture. While epithelial cells primarily seal wounds in 2-dimensional sheets through collective movement along the basement membrane (BM), how they heal injuries in 3-dimensional architecture remains elusive. Using post-radiation anagen hair follicle repair (AHFR) as a model system, we studied how cells repair injuries through multi-photon intravital imaging. Before radiation, the growth of concentric internal structures of hair follicles (HFs) is primarily supported by proliferative germinative/matrix cells surrounding dermal papilla at the base.

944 Non-coding double stranded RNA induces retinoic acid synthesis and retinoid signaling to control regeneration

Wed, 2019-05-01 00:00
Wound induced hair follicle neogenesis (WIHN) is a model of tissue regeneration in adults where hair follicles develop de novo following deep wounding. dsRNA (Poly I:C) generated after wounding activates TLR3 to induce WIHN in mice but mechanisms and translatability are unclear. We first compared the transcriptome of mouse WIHN to human facial rejuvenation after non-ablative laser treatment and find an unexpected signature for both dsRNA and retinoic acid (RA). By transcriptome and proteomic analysis, we also find a highly significant (p<3.6x10ˆ-15 and p<8.2x10ˆ-80, respectively) overlap of upregulated genes in keratinocytes following treatment with dsRNA or RA.

943 Temporal-spatial activation of Wnt-signaling within Type1 / Type 2 immunity during wound healing

Wed, 2019-05-01 00:00
The interaction and activity of Wnt-signaling and immunity at the correct sites and time points must be tightly regulated to achieve propper tissue repair but the cell populations activating Wnt and how they are regulated and interact remain poorly defined. We aimed to analyze the temporal-spatial activation of the canonical Wnt-signaling and expression of Wnt-ligands in different cell populations of the skin under type 1 and type 2 conditions. Murine keratinocytes, fibroblasts and RAW264.7 macrophages were stimulated with cytokines to simulate type 1 and type 2 immunity, RAW264.7 cells were also polarized towards M1 and M2 macrophages and an in vivo full-thickness skin wound model were used to study Wnt activation (using lef-1 expression as readout) and Wnt-ligand expression.

942 Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing

Wed, 2019-05-01 00:00
Mammalian wounds typically heal by fibrotic repair without hair follicle (HF) regeneration. Fibrosis and regeneration are currently considered the opposite end of wound healing. This study sought to determine if scar could be remodeled to promote healing with HF regeneration. Here, we reveal that the activation of the Sonic hedgehog (Shh) pathway reinstalls a regenerative dermal niche, called dermal papilla, which is required and sufficient for HF neogenesis (HFN). Epidermal Shh overexpression or constitutive Smoothened dermal activation results in extensive HFN in wounds that otherwise end in scarring.

941 Epigenetic manipulation of epidermal cells leads to enhanced cellular migration without an increase in cell proliferation

Wed, 2019-05-01 00:00
Cell migration is essential in wound healing and epidermal resurfacing, and more so than cellular proliferation. Given the importance of epigenetics in DNA expression and biologic function, we determined the effect of altering the epigenetic cellular environment to stimulate cell migration. In these experiments, we used HaCaT cells and used various potential therapeutic agents that affect the epigenetic cellular environment. We determined migration by performing monolayer scratch assays and using the IncuCyte S3 Live -Cell Analysis System (Essen Bioscience, Ann Arbor, Michigan) assay system, which allows tissue culture plates and cells to be monitored by imaging and statistical analysis of migration and confluence in a standard tissue culture incubator (95% air, 5% carbon dioxide).

940 Epithelial-microbial crosstalk modifies wound healing outcomes: from shotgun metagenomics to mechanistic understanding

Wed, 2019-05-01 00:00
Impaired wound healing is a major complication of diabetes and threatens to affect approximately one-quarter of the ∼400 million adults worldwide living with diabetes. Diabetic foot ulcer (DFU) complications result in two-thirds of all lower extremity amputations, with 5-year mortality rates surpassing many cancers. While DFUs are colonized with diverse microbes including pathogens, it is unclear how they impact clinical outcomes and the mechanisms by which they alter wound healing responses. To identify strain-level microbial biomarkers influencing clinical outcomes in a longitudinal prospective cohort of 100 subjects with DFU, we integrated metagenomic shotgun sequencing with clinical metadata in a machine learning framework.

939 Anovel dermal hyaluronidase (Cemip) controls reactive adipogenesis and innate immune defense against S. aureus infection

Wed, 2019-05-01 00:00
Hyaluronan (HA) has essential functions in control of immune reactions. Digestion of HA into small fragments occurs following tissue injury and in other inflammatory conditions, resulting in loss of high molecular weight HA (HMW-HA) from the dermis. The mechanism responsible for this loss of HMW-HA has been unknown since expression of classical hyaluronidases does not change after injury. In this study, we investigated a newly discovered hyaluronidase (Cemip), and its role in the innate immune response to S.

938 The skin transcriptome in hidradenitis suppurativa uncovers an antimicrobial and sweat gland gene signature that has distinct overlap with wounded skin

Wed, 2019-05-01 00:00
Hidradenitis suppurativa (HS) is characterized by recurrent abscesses and sinus tract formation leading to chronic non-healing wounds. We analyzed microarray gene expression of HS lesional and non-lesional skin samples (Blok et al., 2016). Differentially expressed genes (DEGs) in HS lesional vs. non-lesional skin were also compared to DEGs in punch-biopsy wounded vs. normal skin (Igelsias-Bertolome et al., 2018). A number of antimicrobial peptides and proteins (AMP), including members of the S100 family (log2FC=4.85, p<0.001), defensins (log2FC=3.75, p<0.001), and interferon stimulated antiviral genes, such as oligoadenylate synthetase 2 (log2FC=1.88, p<0.001), were significantly upregulated in both HS lesional skin and wounded skin.

937 Induction of IL-11 expression leads to persistent abnormal fibroblast activity in cutaneous wound healing

Wed, 2019-05-01 00:00
Injury of the skin can provoke excessive accumulation of extracellular matrix (ECM) leading to a hypertrophic scar or keloid development. However, the mechanism responsible for the persistence of the fibrotic response in a wound healing process is yet not well understood. There is growing evidence that abnormal fibroblast activity mediated by IL-11 signalling plays the pivotal role in systemic organ fibrosis. Therefore, we investigated whether the pathologic activity of myofibroblast-like keloid fibroblast (KFs) are potentiated by hypoxia-induced mesenchymal transition mediated by IL-11.

936 Systemic absorption and safety of topical timolol for chronic wounds

Wed, 2019-05-01 00:00
Chronic wounds pose a major challenge on the health care system, with rising costs and associated morbidities. Better understanding of chronic wound biology and the advancement of technology have led to the use of an array of wound care therapies, including the off-label application of topical timolol for the healing of chronic wounds. Timolol is a non-selective, beta1/beta2 adrenergic receptor antagonist well established for the treatment of glaucoma. Clinical experience has broadened its use for a number of dermatologic indications such as infantile hemangiomas and recently chronic wounds.

935 Clinical manifestations and quality of life in patients with recessive dystrophic epidermolysis bullosa

Wed, 2019-05-01 00:00
Background: Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited chronic blistering disease with multiorgan co-morbidities. Understanding its disease course and effect on quality of life (QOL) serves as an essential reference baseline for emerging RDEB therapies. Method: A prospective, cross-sectional study of self-reported questionnaire responses collected from RDEB patients from Feb 2012 to Oct 2016 through the global EBCare Registry. Wounds were evaluated based on size, chronicity, pain, itch, and severity as defined by impact on performing activities of daily living.

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