ATP-dependent chromatin remodeller brahma related gene 1 promotes keratinocyte migration and modulates cell Signalling during wound healing in human skin.

Skin wound healing is driven by proliferation, migration and differentiation of several cell types that are controlled by the alterations in the gene expression programmes. Brahma Gene 1 (BRG1) (also known as SMARCA4) is a core ATPase in the BRG1 Associated Factors (BAF) ATP-dependent chromatin remodelling complexes that alter DNA-histone interaction in chromatin at the specific gene regulatory elements resulting in increase or decrease of the target gene transcription. Using siRNA mediated suppression of BRG1 during wound healing in a human ex vivo and in vitro (scratch assay) models, we demonstrated that BRG1 is essential for efficient skin wound healing by promoting epidermal keratinocytes migration, but not their proliferation or survival.

Mechanical epilation exerts complex biological effects on human hair follicles and perifollicular skin: An ex vivo study approach.

Objective: Electrical epilation of unwanted hair is a widely used hair removal method, but it is largely unknown how this affects the biology of human hair follicles (HF) and perifollicular skin. Here, we have begun to explore how mechanical epilation changes selected key biological read-out parameters ex vivo within and around the pilosebaceous unit.

Methods: Human full-thickness scalp skin samples were epilated ex vivo using an electro-mechanical device, organ-cultured for up to 6 days in serum-free, supplemented medium, and assessed at different time points by quantitative (immuno-)histomorphometry for selected relevant read-out parameters in epilated and sham-epilated control samples.

Highlighting nuances of blue light phototherapy: Mechanisms and safety considerations.

The efficacy of blue light therapy in dermatology relies on numerous clinical studies. The safety remains a topic of controversy, where potentially deleterious effects were derived from in vitro rather than in vivo experiments. The objectives of this work were (1) to highlight the nuances behind "colors" of blue light, light propagation in tissue and the plurality of modes of action; and (2) to rigorously analyze studies on humans reporting both clinical and histological data from skin biopsies with focus on DNA damage, proliferation, apoptosis, oxidative stress, impact on collagen, elastin, immune cells, and pigmentation.

Skin Aging in Long-Lived Naked Mole-Rats Is Accompanied by Increased Expression of Longevity-Associated and Tumor Suppressor Genes.

Naked mole-rats (NMRs) (Heterocephalus glaber) are long-lived mammals that possess a natural resistance to cancer and other age-related pathologies, maintaining a healthy life span >30 years. In this study, using immunohistochemical and RNA-sequencing analyses, we compare skin morphology, cellular composition, and global transcriptome signatures between young and aged (aged 3‒4 vs. 19‒23 years, respectively) NMRs.

Evidence for a functional interaction of WNT10A and EBF1 in male-pattern baldness.

More than 300 genetic risk loci have been identified for male pattern baldness (MPB) but little is known about the exact molecular mechanisms through which the associated variants exert their effects on MPB pathophysiology. Here, we aimed at further elucidating the regulatory architecture of the MPB risk locus on chromosome (chr.) 2q35, where we have previously reported a regulatory effect of the MPB lead variant on the expression of WNT10A.

Cryptochrome 1 is modulated by blue light in human keratinocytes and exerts positive impact on human hair growth.

Photoactivation of cryptochrome-family proteins by blue light is a well-established reaction regulating physiology of plants, fungi, bacteria, insects and birds, while impact of blue light on cryptochrome synthesis and/or activity in human non-visual cells remains unknown. Here, we show that 453 nm blue light induces cryptochrome 1 (CRY1) accumulation in human keratinocytes and the hair follicle. CRY1 is prominently expressed in the human anagen hair follicle, including epithelial stem cells.

Plucked hair follicles from patients with chronic discoid lupus erythematosus show a disease-specific molecular signature.

Objective: When faced with clinical symptoms of scarring alopecia-the standard diagnostic pathway involves a scalp biopsy which is an invasive and expensive procedure. This project aimed to assess if plucked hair follicles (HFs) containing living epithelial cells can offer a non-invasive approach to diagnosing inflammatory scalp lesions.

Methods: Lesional and non-lesional HFs were extracted from the scalp of patients with chronic discoid lupus erythematosus (CDLE), psoriasis and healthy controls.

Bridging the "Dead Hair"-"Live Follicle" Divide in Applied Hair Research.

For many decades, applied hair research has been hampered by an unproductive intellectual and conceptual divide between researchers who are primarily interested in the hair shaft (HS), its structural properties, visual appearance and cosmetic manipulation, and those investigators who are mainly interested in the fascinating miniorgan that cyclically regenerates the HS, the hair follicle (HF). This article attempts to bridge this unproductive divide between the "dead hair" and "live follicle" worlds by summarizing both current key concepts and major open questions on how the HF, namely, the anagen hair bulb and its precortical hair matrix keratinocytes, generate the HS, focusing on selected key signaling pathways. We discuss current theories of hair shape formation and avenues toward impacting on human HS structure.

Transepidermal UV radiation of scalp skin ex vivo induces hair follicle damage that is alleviated by the topical treatment with caffeine.

Objectives: Although the effect of ultraviolet radiation (UVR) on human skin has been extensively studied, very little is known on how UVR impacts on hair follicle (HF) homeostasis. Here, we investigated how solar spectrum UVR that hits the human skin surface impacts on HF biology, and whether any detrimental effects can be mitigated by a widely used cosmetic and nutraceutical ingredient, caffeine.

Methods: Human scalp skin with terminal HFs was irradiated transepidermally ex vivo using either 10 J/cm UVA (340-440 nm) + 20 mJ/cm UVB (290-320 nm) (low dose) or 50 J/cm UVA + 50 mJ/cm UVB (high dose) and organ-cultured under serum-free conditions for 1 or 3 days.

Light-based home-use devices for hair removal: Why do they work and how effective they are?

Objectives: This review has the following objectives: Firstly, it provides an explanation of the evolution of laser/intense pulsed light (IPL) hair reduction modalities from high fluence professional devices to low fluence home-use appliances. Secondly, it summarises published literature reviews on home-use devices (HUDs) as evidence of their growing credibility. Thirdly, it proposes mechanistic differences in light delivery regimes and the resulting divergences in mode of action.

Differential response of human dermal fibroblast subpopulations to visible and near-infrared light: Potential of photobiomodulation for addressing cutaneous conditions.

Background Objectives: The past decade has witnessed a rapid expansion of photobiomodulation (PBM), demonstrating encouraging results for the treatment of cutaneous disorders. Confidence in this approach, however, is impaired not only by a lack of understanding of the light-triggered molecular cascades but also by the significant inconsistency in published experimental outcomes, design of the studies and applied optical parameters. This study aimed at characterizing the response of human dermal fibroblast subpopulations to visible and near-infrared (NIR) light in an attempt to identify the optical treatment parameters with high potential to address deficits in aging skin and non-healing chronic wounds.

Genome-Wide MicroRNA Analysis Implicates miR-30b/d in the Etiology of Alopecia Areata.

Alopecia areata (AA) is one of the most common forms of human hair loss. Although genetic studies have implicated autoimmune processes in AA etiology, understanding of the etiopathogenesis is incomplete. Recent research has implicated microRNAs, a class of small noncoding RNAs, in diverse autoimmune diseases.

Exploring a Role for Regulatory miRNAs In Wound Healing during Ageing:Involvement of miR-200c in wound repair.

Multiple factors and conditions can lead to impaired wound healing. Chronic non-healing wounds are a common problem among the elderly. To identify microRNAs negatively impacting the wound repair, global miRNA profiling of wounds collected from young and old mice was performed.

Photobiomodulation of human dermal fibroblasts in vitro: decisive role of cell culture conditions and treatment protocols on experimental outcome.

Photobiomodulation-based (LLLT) therapies show tantalizing promise for treatment of skin diseases. Confidence in this approach is blighted however by lamentable inconsistency in published experimental designs, and so complicates interpretation. Here we interrogate the appropriateness of a range of previously-reported treatment parameters, including light wavelength, irradiance and radiant exposure, as well as cell culture conditions (e.

A new path in defining light parameters for hair growth: Discovery and modulation of photoreceptors in human hair follicle.

Background And Objective: Though devices for hair growth based on low levels of light have shown encouraging results, further improvements of their efficacy is impeded by a lack of knowledge on the exact molecular targets that mediate physiological response in skin and hair follicle. The aim of this study was to investigate the expression of selected light-sensitive receptors in the human hair follicle and to study the impact of UV-free blue light on hair growth ex vivo.

Material And Methods: The expression of Opsin receptors in human skin and hair follicles has been characterized using RT-qPCR and immunofluorescence approaches.

The Molecular Revolution in Cutaneous Biology: Noncoding RNAs: New Molecular Players in Dermatology and Cutaneous Biology.

Progress in genome sequencing achieved during the last two decades revealed that only about 2% of the genome codes for proteins, while the largest genome fraction is encoding thousands of non-coding RNAs. Non-coding RNAs play indispensable roles in regulating the activity and stability of the genome. Recent research in the area of the non-coding transcriptome signified the crucial roles for RNA regulatory networks in the normal development and their implications in a variety of pathological conditions.

Photobiomodulation devices for hair regrowth and wound healing: a therapy full of promise but a literature full of confusion.

Photobiomodulation is reported to positively influence hair regrowth, wound healing, skin rejuvenation and psoriasis. Despite rapid translation of this science to commercial therapeutic solutions, significant gaps in our understanding of the underlying processes remain. The aim of this review was to seek greater clarity and rationality specifically for the selection of optical parameters for studies on hair regrowth and wound healing.

MicroRNAs (miRNAs) in the control of HF development and cycling: the next frontiers in hair research.

Hair follicle development and its postnatal regeneration are characterized by dramatic changes in its microanatomy and cellular activity, which are controlled by multiple signalling pathways, transcription factors and epigenetic regulators, including microRNAs (miRNAs). miRNAs and their targets form remarkably diverse regulatory networks, playing a key role in the execution of gene expression programmes in the different cell lineages of the hair follicle. This review summarizes the roles of miRNAs in the control of hair follicle development, cycling and hair pigmentation, emphasizes the remaining problems/unanswered questions, and provides future directions in this rapidly growing and exciting area of research.

MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway.

Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production.

Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy.

Chemotherapy has severe side effects in normal rapidly proliferating organs, such as hair follicles, and causes massive apoptosis in hair matrix keratinocytes followed by hair loss. To define the molecular signature of hair follicle response to chemotherapy, human scalp hair follicles cultured ex vivo were treated with doxorubicin (DXR), and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in DXR-treated hair follicles versus controls.

Bone morphogenetic protein signaling suppresses wound-induced skin repair by inhibiting keratinocyte proliferation and migration.

Bone morphogenetic protein (BMP) signaling plays a key role in the control of skin development and postnatal remodeling by regulating keratinocyte proliferation, differentiation, and apoptosis. To study the role of BMPs in wound-induced epidermal repair, we used transgenic mice overexpressing the BMP downstream component Smad1 under the control of a K14 promoter as an in vivo model, as well as ex vivo and in vitro assays. K14-caSmad1 (transgenic mice overexpressing a constitutively active form of Smad1 under K14 promoter) mice exhibited retarded wound healing associated with significant inhibition of proliferation and increased apoptosis in healing wound epithelium.