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Editorial note: Welcome to the Journal of Investigative Dermatology (JID) SnapshotDx Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical images above, while additional questions concern the findings reported in the JID article by Rahbar et al. (https://doi.org/10.1016/j.jid.2017.11.035).
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image above, while additional questions concern the findings reported in a JID article by Tucker et al (https://doi.org/10.1016/j.jid.2018.01.021).
Zebrafish represent a powerful model system with which to study human biology and pathology. Recently developed CRISPR/Cas9 technology enables genetic manipulation with precision. Using CRISPR/Cas9 methodology, van Gils et al. generated knockout zebrafish for abcc6a, the orthologue of human ABCC6 that is mutated in pseudoxanthoma elasticum. Although similarities exist between this and other abcc6a zebrafish models, none fully recapitulate phenotypes of human pseudoxanthoma elasticum.
Pannexin-3 (Panx3) is a gap junction protein and is required for regulating cell cycle exit and the differentiation of osteoblasts and chondrocytes during skeletal development. However, the role of Panx3 in skin tissue regeneration remains unclear. Following dorsal skin punch biopsies, Panx3 knockout mice exhibited a significant delay in wound healing with insufficient re-epithelialization, decreased inflammatory reaction and reduced collagen remodeling. Panx3 expression coincided with inflammatory reactions both in vivo and in vitro.
Population-based estimates on the prevalence of atopic dermatitis in adults vary widely. The objectives of the present study were to determine the prevalence of atopic dermatitis in the population of the United States, distribution of disease severity, and assess its impact on health-related quality of life. Among 1,278 participating adults, the prevalence (95%CI) of atopic dermatitis was 7.3% (5.9-8.8). 60.1% (56.1-64.1%) of participants were classified as mild 28.9% (25.3-32.7%) as moderate and 11% as severe (8.6-13.7%).
Activation of the transcription factor, the aryl hydrocarbon receptor (AHR), in normal human epidermal keratinocytes (NHEKs) increased AHR binding in the promoters of the glucose transporter, SLC2A1, and the glycolytic enzyme, enolase 1 (ENO1). This increased chromatin binding corresponded with AHR-dependent decreases in levels of SLC2A1 and ENO1 mRNA, protein and activities. Studies of the ENO1 promoter showed activation of the AHR decreases the transcription of ENO1. Glycolysis was lowered by activation of the AHR as measured by decreases in glucose uptake and the production of pyruvate and lactate.
The heritable forms of epidermolysis bullosa (EB), a phenotypically heterogeneous group of skin fragility disorders, is currently associated with mutations in as many as 21 distinct genes. EB is primarily a disorder affecting the epithelial layers of skin and mucous membranes, without extracutaneous manifestations, and thus being non-syndromic. However, recent demonstrations of skin blistering in the spectrum of EB in multisystem disorders with single gene defects highlight the concept of syndromic EB.
Skin cancer is the most frequently diagnosed cancer in the US, and solar ultraviolet (UV) radiation is an established causative factor for ∼90% of these cases. Despite efforts aimed at UV protection, including use of sunscreen and clothing, annual cases of skin cancers continue to rise. Here, we report that dietary grape powder (GP) mitigates UVB-mediated skin carcinogenesis in SKH-1 hairless mouse model. Employing a UVB initiation-promotion protocol, where mice were exposed to 180 mJ/cm2 UVB 2x/week for 28 weeks, we determined the effects of GP-fortified diet (3% or 5%) on skin carcinogenesis.
Loss of E-cadherin and concomitant up-regulation of N-cadherin is known as the cadherin switch and has been implicated in melanoma progression. Mechanistically, homophilic ligation of N-cadherin-expressing melanoma cells with N-cadherin presented within the micro-environment is thought to facilitate invasion. However, the biophysical aspects governing molecular specificity and function of such interactions remain unclear. By using precisely defined nano-patterns of N- or E-cadherin (with densities tunable by more than one order of magnitude, from 78 to 1,128 ligands/μm2), we analyzed adhesion and spreading of six different human melanoma cell lines with distinct constitutive cadherin expression patterns.
Adiponectin is known to have beneficial effects on lipid and insulin metabolism, wound healing, and cellular senescence, but its effect on skin barrier formation remains unknown. We investigated the effects of adiponectin on keratinocyte lipid synthesis with respect to skin barrier function. Lipid staining revealed an adiponectin-mediated increase in keratinocyte intracellular and reconstructed epidermal lipid content. Moreover, significant increases in the levels of ceramide and its downstream metabolites (sphingosine and sphingosine-1-phosphate) following adiponectin stimulation were detected using liquid chromatography–mass spectrometry.
Dendritic cells (DC) express the ecto-5'-nucleotidase CD73 that generates immunosuppressive adenosine (Ado) by dephosphorylation of extracellular adenosine mono- and -diphosphate. To investigate whether CD73-derived Ado has immune suppressive activity, 2,4-dinitrothiocyanobenzene (DNTB) was applied to skin of wildtype (WT) or CD73 deficient (CD73-/-) mice, followed by sensitization and challenge with 2,4-dinitrofluorobenzene (DNFB). In this model we demonstrate induction of tolerance by DNTB against DNFB only in W T but not in CD73-/- mice.
Much of our understanding of human biology and the function of mammalian cells in tissue regeneration have been derived from mechanistically and genetically manipulated rodent models. However, current models examining epidermal wound repair fail to simultaneously address both the cross-species mechanistic and immunogenic differences. Herein, we describe a multifaceted approach intended to better recapitulate human skin recovery in rodent models. First, immunodeficient NSG mice were intravenously inoculated with human hematopoietic stem cells to become in essence, humanized, and capable of initiating an adaptive immune response.
Dendritic cell-associated C-type lectin-2 (Dectin-2) recognizes fungal polysaccharides, including α-mannan. Dectin-2-mediated recognition of fungi, such as Candida albicans, leads to NF-κB activation, which induces production of inflammatory cytokines. However, Dectin-2’s role in skin wound healing remains unclear. In this study, we sought to determine how Dectin-2 deficiency and the administration of α-mannan affected the wound healing process. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and Dectin-2-deficient (KO) mice.
Aging is characterized by accumulation of chronic and irreversible oxidative damage, chronic inflammation, and organ dysfunction. Superoxide dismutase (SOD) serves as a major enzyme for cellular superoxide radical metabolism and physiologically regulates cellular redox balance throughout the body. The copper/zinc superoxide dismutase (SOD1)-deficient mice showed diverse phenotypes associated with enhanced oxidative damage in whole organs. Here, we found that oral treatment with syringaresinol (SYR, also known as lirioresinol B), which is the active component in the berries of Korean ginseng (Panax ginseng C.A.Meyer), attenuated the age-related changes in Sod1-/- skin.
α-Calcitonin gene-related protein (α-CGRP) is synthesized by sensory nerves in the dermis and its release can cause vasodilatation and local inflammation. Its vasorelaxant effects are based on the direct activation of smooth muscle and endothelial cells as well as the activation of mast cells causing the release of vasoactive and proinflammatory mediators. Here, we show that in the capsaicin model for neurogenic inflammation capsaicin-induced edema formation is mediated by α-CGRP and mast cells but is absent in thromboxane receptor (TP)-deficient mice.
Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are autoimmune bullous skin diseases. DH has been described to evolve into BP and the two diseases can have overlapping clinical appearances and diagnostic findings, but the association between DH and BP has not previously been studied in a large population. To evaluate DH and celiac disease (CD) as risk factors for BP we conducted a retrospective case-control study of patients with BP and matched controls with basal cell carcinoma diagnosed in Finland between 1997 and 2013.