Journal Of Investigative Dermatology

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659 Towards functional analysis of prolylcarboxypeptidase in human skin - a regulator of alpha-MSH activity?

Sun, 2019-09-01 00:00
Prolylcarboxypeptidase (PRCP) is s serine protease that recently emerged as a regulator of the central melanocortin system, i. e. control of food intake and energy metabolism, by degrading α-MSH (1-13) into biologically inactive α-MSH (1-12). Therefore, we wondered if PRCP may also play a role in regulation of the peripheral melanocortin system. As a first step towards answering this question we examined the expression of PRCP in various cutaneous cell types at RNA and protein level in vitro. PRCP transcripts were detected in normal human melanocytes, normal human keratinocytes and human dermal fibroblasts (HDFs) from different donors as shown by endpoint reverse transcriptase- polymerase chain reaction (RT-PCR).

658 Modulating NFkB signaling in skin wounds through pharmacological or probiotic intervention using Faecalibacterium prausnitzii extracts

Sun, 2019-09-01 00:00
Chronic leg ulcers are a major health burden globally, increasing in incidence with ageing and morbidity from diabetes. A common mechanism highlighted in chronic hard to heal wounds is exaggerated and sustained inflammation which inhibits the closure and therefore represents a therapeutic target. In the present study, we analyzed the effect of supernatant extracted from two strains of Faecalibacterium prausnitzii, a commensal gut microbiome known to have anti-inflammatory activity. C57BL/6 wild type mice were subjected to full thickness excisional wounds and randomized for treatment by extracts from SPA2 or SPAH strains versus vehicle control.

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

Sun, 2019-09-01 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.

656 Immune cell profiling of wounds from Epidermolysis bullosa patients

Sun, 2019-09-01 00:00
Epidermolysis bullosa or EB, is a group of genetic diseases characterized by excessive skin fragility causing blisters with minimum trauma. In severe EB patients, blisters can develop into nonhealing wounds, which besides being extremely painful, are the starting point to other more severe – and deadly – clinical manifestations, such as systemic infections and cancer. The current state of research points towards EB being a combination of a heritable skin and inflammatory disease. However, the impact of host immune dysregulation has not been explored in the context of wound resolution.

655 Skullcapflavone II Inhibits Degradation of Type I Collagen by Suppressing MMP-1 Transcription in Human Skin Fibroblasts

Sun, 2019-09-01 00:00
Skullcapflavone II is a flavonoid derived from the root of Scutellaria baicalensis, an herbal medicine used for anti-inflammatory and anti-cancer therapies. We analyzed the effect of skullcapflavone II on the expression of matrix metalloproteinase-1 (MMP-1) and integrity of type I collagen in foreskin fibroblasts. Skullcapflavone II did not affect the secretion of type I collagen but reduced the secretion of MMP-1 in a dose- and time-dependent manner. Real-time reverse transcription-PCR and reporter gene assays showed that skullcapflavone II reduced MMP-1 expression at the transcriptional level.

654 Stimulation and Protection of Cutaneous Sensory Neuron System induced by Forest Honey from Ikaria Island

Sun, 2019-09-01 00:00
Sensory innervation involves nerve endings which are located in dermis and epidermis, reaching the uppermost viable layer of skin. Cutaneous innervation is closely linked with major skin functions and contributes to skin homeostasis. Wound-healing, repair process, sense of touch, perception of thermal stimuli as well as intra-epidermal nerve fibre density on face decrease with aging and are associated with changes in neuronal functions and structures. For centuries, honey has been utilized for wound healing purposes but recently, information regarding honey’s mechanisms of action on wound healing and as a therapeutic agent for skin disorders has accumulated at a rapid pace.

653 Topical use of exosomes from human maternal milk accelerates acute cutaneous wound healing

Sun, 2019-09-01 00:00
Cutaneous wound healing is a complex but highly efficient process. Under certain pathologic conditions healing may be impaired, thus lengthening the process and eventually leading to repeated medical intervention and wound chronicity. Exosomes (secreted extracellular vesicles) are present in biological fluids where they exert a key role in intercellular communication at the tissue, organ and organismal levels. Since human breast milk presents abundant maternal extracellular vesicles (MEVs) with immunomodulatory and pro-regenerative properties, in the present study we aimed to evaluate if topical application of MEVs into open wounds would be beneficial for healing.

652 Efficacy and Safety of Autologous Fibroblast Injection for the Treatment of Acne Scars: A 6-month Prospective, Randomized Controlled Study

Sun, 2019-09-01 00:00
Inducing collagen synthesis and remodeling is crucial to achieving optimal clinical improvement in acne scar treatment. Cell therapy with autologous fibroblast can be an alternative treatment option for depressive acne scars. The objective was to investigate the effect of autologous fibroblast treatment of moderate to severely depressed acne scars, a 6-month prospective, a randomized control study was performed at tertiary medical centers. This study was conducted based on a 6-month, prospective, randomized controlled study to compare the effect of autologous fibroblast injection for atrophic acne scar.

651 Efficacy of topical insulin therapy in chronic trophic ulcers over plantar region of leprosy patients – a randomized single blind placebo controlled interventional pilot study

Sun, 2019-09-01 00:00
(a) Chronic trophic ulcers (CTU) especially located over plantar region are leading cause of deformity and disability in Hansen’s patients. Despite various treatment modalities available, it’s quite chronic and refractory to treatment. The successful use of topical insulin in various types of wounds led us to evaluate its safety and efficacy in the treatment of chronic trophic ulcers over the plantar region. (b) Forty two patients released from treatment of leprosy were recruited and randomized in two groups.

650 Topical application of a bacterial lysate modulates changes to the fibrillin-rich microfibril network

Sun, 2019-09-01 00:00
The skin is the human body’s largest organ and is occupied by a highly diverse microbiome. It is well established that certain species of probiotic bacteria confer health benefits to the human gut, such as epithelial repair, enhancement of the gut barrier and modulation of the immune response. However, recent research is starting to uncover potential benefits of probiotic bacteria and their extracts to influence skin health and disease. Previous work in our lab has shown that lysates of commensal bacteria, Lactobacillus rhamnosus GG (LGG), when applied to primary human keratinocytes enhance Tight Junctions and increase proliferation and migration of keratinocytes in scratch assays.

649 Hypoxia-pretreatment as a possible approach to stimulate wound healing potentials of dermal fibroblasts in treatment of chronic skin ulcers

Sun, 2019-09-01 00:00
The development of new therapeutic approaches to chronic wounds hasn’t lost its relevance. In non-healing diabetic ulcers (diabetic foot) auto-transplantation (a common treatment approach) is not effective due to impaired fibroblast functionality and shifts in synthesis of ECM proteins (COL1, COL3, FN) and certain growth factors. It was shown that HIF1 (hypoxia-induced factor) is a key regulator of ECM remodeling by fibroblasts through control of collagen prolyl hydroxylase (P4HA1, P4HA2 – both required for collagen deposition) and lysylhydroxylase (PLOD2 – modulates collagen fibers strength) expression.

648 Adipose-derived stem cells in wound healing: comparison with fibroblasts and keratinocytes interaction

Sun, 2019-09-01 00:00
Adipose-derived stem cells (ADSCs) are a particular subset of mesenchymal stem cells present in the stromal-vascular fraction of the adipose tissue. These cells are considered very attractive for their relative abundance and accessibility in the human body. Keratinocytes and fibroblasts cells play important roles in the skin-wound healing process and are the cell types activated by trauma. The aim of our study was focused to evaluate ADSCs ability to build a dermal matrix to be potentially used as a dermal substitute in the field of wound healing.

647 Investigating re-epithelialization in a novel ex vivo human skin model

Sun, 2019-09-01 00:00
Although numerous wound healing models have been established, a model to study re-epithelialization in vitro, without disrupting the underlying dermal compartment, is lacking. Therefore, we established a new standardized human ex vivo model based on application of negative pressure, inducing blistering and consequently dermal epidermal separation. Effects of this treatment for epidermal regeneration and immune cells were investigated. Immunostaining revealed type IV collagen expression on the remaining dermal compartment, indicating that the basement membrane and thus the underlying dermis remained intact after removal of the blister roof epidermis.

646 Characterization of platelets-derived compounds that induce antimicrobial peptides in human keratinocytes

Sun, 2019-09-01 00:00
The use of formulations based on thrombocyte concentrate lysates (platelet-released growth factors, PRGF) revealed promising effects in the treatment of chronic wounds. The underlying mechanisms are not well understood. We could show that PRGF induced the expression of antimicrobial peptides (AMPs) such as the human beta-defensin-2 and -3 (hBD-2, hBD-3) in keratinocytes which may contribute to the observed beneficial effects of PRGF-based formulations in wound treatment. Given that it is unclear which components of platelets induce AMPs in keratinocytes we aimed to biochemically identify PRGF-derived factors that induce hBD-2 in human keratinocytes.

645 Study of the impact of age-related alterations of the extracellular matrix on the organization of the network of endothelial cells using an in vitro cell co-culture model

Sun, 2019-09-01 00:00
With age, dermis loose its elasticity. Its main component, Collagen, undergo decreased synthesis and degradation. Elastin and Fibronectin are also impacted. In addition, the extrafibrillar matrix shows decreased level of glycosaminoglycans, one of its abundant components. Fibroblasts, key players in the production and organisation of the extracellular matrix (ECM), present reduced growth and modified secretion patterns. Another aspect of ageing is the alteration of the microcirculation network that limits supply of nutrient to the dermis.

644 Papillary and reticular fibroblasts generate specific microenvironments in vitro that impact their angiogenic profile

Sun, 2019-09-01 00:00
Human dermis is divided between the superficial papillary dermis and the deeper reticular dermis that show distinct extracellular matrix (ECM) and vasculature. Papillary and reticular fibroblasts have distinct phenotype and gene signature but the contribution of each subtype of fibroblasts in the generation of specific ECM and vasculature is poorly documented. This study aimed to determine if papillary and reticular fibroblasts generate specific microenvironments in vitro when cultivated as cell sheet and evaluate their impact on angiogenesis.

643 Heat stimuli induces beige adipocytes differentiation and browning of the subcutaneous fat tissues in human skin

Sun, 2019-09-01 00:00
Brown adipocytes as well as beige adipocytes in white adipose tissues (WATs) can dissipate energy via adaptive non-shivering thermogenesis, and play a critical role in the regulation of energy balance. It is well known that cold exposure induces beiging/browning, which is defined as the emergence of beige adipocytes in WATs. Here we investigated whether heat stimuli induces beiging/browning of subcutaneous (SC) fat tissue in vitro and in vivo. Heat stimuli (>39 °C) to differentiated primary human SC adipocytes lowered triglycerides (TG) contents, similar to those exposed to cold stimuli (4, 15 °C).

642 WITHDRAWN

Sun, 2019-09-01 00:00

641 Cell – collagen interactions through collagen-binding integrins are dispensable for murine development

Sun, 2019-09-01 00:00
Collagens are the most abundant component of the extracellular matrix. They largely contribute to tissue mechanical stability. In the skin, integrins α1β1, α2β1, α11β1 are the three main collagen receptors facilitating cell to collagen contact. Using single and double knockout mouse models lacking collagen-binding integrins, we were able to delineate their individual functions and functional redundancy. Here we address the overall significance of integrin-mediated direct interaction of cells with collagens.

640 Suppressive effect of HMGB1 A-box for inflammation in keratinocytes

Sun, 2019-09-01 00:00
“High mobility group box 1” (HMGB1) is a well-known nuclear protein that stabilizes DNA and facilitates gene transcription, but at outside the membrane, it functions as an alarmin, causing an inflammatory response in combination with other cytokines. Recently, we confirmed that HMGB1 shows the proinflammatory activity depending on the redox status, which is in the reduced, disulfide, or oxidized form. The reduced-HMGB1 exerts a chemoattractive effect, and the disulfide-HMGB1 has proinflammatory cytokine activity, but the oxidized form has no inflammatory activity.

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