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Vitamin C-squalene bioconjugate promotes epidermal thickening and collagen production in human skin.Scientific Reports Oct 2020Vitamin C (Vit C) benefits to human skin physiology notably by stimulating the biosynthesis of collagen. The main cutaneous collagens are types I and III, which are less...
Vitamin C (Vit C) benefits to human skin physiology notably by stimulating the biosynthesis of collagen. The main cutaneous collagens are types I and III, which are less synthesized with aging. Vit C is one of the main promotors of collagen formation but it poorly bypasses the epidermis stratum corneum barrier. To address this challenge, we developed a lipophilic version of Vit C for improving skin diffusion and delivery. Vit C was covalently conjugated to squalene (SQ), a natural lipid of the skin, forming a novel Vit C-SQ derivative suitable for cream formulation. Its biological activity was investigated on human whole skin explants in an ex vivo model, through histology and protein and gene expression analyses. Results were compared to Vit C coupled to the reference lipophilic compound palmitic acid, (Vit C-Palmitate). It was observed that Vit C-SQ significantly increased epidermal thickness and preferentially favored collagen III production in human skin after application for 10 days. It also promoted glycosaminoglycans production in a higher extent comparatively to Vit C-Palmitate and free Vit C. Microdissection of the explants to separate dermis and epidermis allowed to measure higher transcriptional effects either in epidermis or in dermis. Among the formulations studied, the strongest effects were observed with Vit C-SQ.
Topics: Adult; Ascorbic Acid; Collagen; Drug Compounding; Drug Delivery Systems; Epidermis; Female; Humans; In Vitro Techniques; Skin; Squalene
PubMed: 33037252
DOI: 10.1038/s41598-020-72704-1 -
Cell Reports Oct 2018Epithelial tissues, such as the skin, rely on cellular plasticity of stem cells (SCs) from different niches to restore tissue function after injury. How these...
Epithelial tissues, such as the skin, rely on cellular plasticity of stem cells (SCs) from different niches to restore tissue function after injury. How these molecularly and functionally diverse SC populations respond to injury remains elusive. Here, we genetically labeled Lgr5- or Lgr6-expressing cells from the hair follicle bulge and interfollicular epidermis (IFE), respectively, and monitored their individual transcriptional adaptations during wound healing using single-cell transcriptomics. Both Lgr5 and Lgr6 progeny rapidly induced a genetic wound signature that, for Lgr5 progeny, included the remodeling of receptors to permit interactions with the wound environment, a property that Lgr6 progeny possessed even before wounding. When contributing to re-epithelialization, Lgr5 progeny gradually replaced their bulge identity with an IFE identity, and this process started already before Lgr5 progeny left the bulge. Altogether, this study reveals how different SCs respond and adapt to a new environment, potentially explaining cellular plasticity of many epithelial tissues.
Topics: Animals; Cell Proliferation; Cells, Cultured; Epidermis; Female; Hair Follicle; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Re-Epithelialization; Receptors, G-Protein-Coupled; Single-Cell Analysis; Skin; Stem Cells; Transcriptome; Wound Healing
PubMed: 30332640
DOI: 10.1016/j.celrep.2018.09.059 -
International Journal of Molecular... Feb 2023The skin is the largest organ of the body and consists of an epidermis, dermis and subcutaneous adipose tissue. The skin surface area is often stated to be about 1.8 to... (Review)
Review
The skin is the largest organ of the body and consists of an epidermis, dermis and subcutaneous adipose tissue. The skin surface area is often stated to be about 1.8 to 2 m and represents our interface with the environment; however, when one considers that microorganisms live in the hair follicles and can enter sweat ducts, the area that interacts with this aspect of the environment becomes about 25-30 m. Although all layers of the skin, including the adipose tissue, participate in antimicrobial defense, this review will focus mainly on the role of the antimicrobial factors in the epidermis and at the skin surface. The outermost layer of the epidermis, the stratum corneum, is physically tough and chemically inert which protects against numerous environmental stresses. It provides a permeability barrier which is attributable to lipids in the intercellular spaces between the corneocytes. In addition to the permeability barrier, there is an innate antimicrobial barrier at the skin surface which involves antimicrobial lipids, peptides and proteins. The skin surface has a low surface pH and is poor in certain nutrients, which limits the range of microorganisms that can survive there. Melanin and trans-urocanic acid provide protection from UV radiation, and Langerhans cells in the epidermis are poised to monitor the local environment and to trigger an immune response as needed. Each of these protective barriers will be discussed.
Topics: Epidermis; Skin; Epidermal Cells; Langerhans Cells; Lipids
PubMed: 36834554
DOI: 10.3390/ijms24043145 -
Frontiers in Immunology 2021The epidermis constitutes a continuous external layer covering the body, offering protection against bacteria, the most abundant living organisms that come into contact... (Review)
Review
The epidermis constitutes a continuous external layer covering the body, offering protection against bacteria, the most abundant living organisms that come into contact with this barrier. The epidermis is heavily colonized by commensal bacterial organisms that help protect against pathogenic bacteria. The highly regulated and dynamic interaction between the epidermis and commensals involves the host's production of nutritional factors promoting bacterial growth together to chemical and immunological bacterial inhibitors. Signal trafficking ensures the system's homeostasis; conditions that favor colonization by pathogens frequently foster commensal growth, thereby increasing the bacterial population size and inducing the skin's antibacterial response, eliminating the pathogens and re-establishing the normal density of commensals. The microecological conditions of the epidermis favors Gram-positive organisms and are unsuitable for long-term Gram-negative colonization. However, the epidermis acts as the most important host-to-host transmission platform for bacteria, including those that colonize human mucous membranes. Bacteria are frequently shared by relatives, partners, and coworkers. The epidermal bacterial transmission platform of healthcare workers and visitors can contaminate hospitalized patients, eventually contributing to cross-infections. Epidermal transmission occurs mostly the hands and particularly through fingers. The three-dimensional physical structure of the epidermis, particularly the fingertips, which have frictional ridges, multiplies the possibilities for bacterial adhesion and release. Research into the biology of bacterial transmission the hands is still in its infancy; however, tribology, the science of interacting surfaces in relative motion, including friction, wear and lubrication, will certainly be an important part of it. Experiments on finger-to-finger transmission of microorganisms have shown significant interindividual differences in the ability to transmit microorganisms, presumably due to genetics, age, sex, and the gland density, which determines the physical, chemical, adhesive, nutritional, and immunological status of the epidermal surface. These studies are needed to optimize interventions and strategies for preventing the hand transmission of microorganisms.
Topics: Bacteria; Bacterial Infections; Epidermis; Fingers; Hand; Humans; Microbiota
PubMed: 34925344
DOI: 10.3389/fimmu.2021.774018 -
Biochimica Et Biophysica Acta Mar 2014Ceramide, the backbone structure of all sphingolipids, as well as a minor component of cellular membranes, has a unique role in the skin, by forming the epidermal... (Review)
Review
Ceramide, the backbone structure of all sphingolipids, as well as a minor component of cellular membranes, has a unique role in the skin, by forming the epidermal permeability barrier at the extracellular domains of the outermost layer of the skin, the stratum corneum, which is required for terrestrial mammalian survival. In contrast to the role of ceramide in forming the permeability barrier, the signaling roles of ceramide and its metabolites have not yet been recognized. Ceramide and/or its metabolites regulate proliferation, differentiation, and apoptosis in epidermal keratinocytes. Recent studies have further demonstrated that a ceramide metabolite, sphingosine-1-phosphate, modulates innate immune function. Ceramide has already been applied to therapeutic approaches for treatment of eczema associated with attenuated epidermal permeability barrier function. Pharmacological modulation of ceramide and its metabolites' signaling can also be applied to cutaneous disease prevention and therapy. The author here describes the signaling roles of ceramide and its metabolites in mammalian cells and tissues, including the epidermis. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
Topics: Animals; Apoptosis; Cell Differentiation; Cell Proliferation; Ceramides; Eczema; Epidermis; Humans; Permeability; Signal Transduction
PubMed: 24055887
DOI: 10.1016/j.bbalip.2013.09.003 -
Seminars in Immunopathology Nov 2019Pemphigoid diseases are a group of autoimmune blistering skin diseases defined by an immune response against certain components of the dermal-epidermal adhesion complex.... (Review)
Review
Pemphigoid diseases are a group of autoimmune blistering skin diseases defined by an immune response against certain components of the dermal-epidermal adhesion complex. They are prototypical, autoantibody-driven, organ-specific diseases with the emergence of inflammatory skin lesions dependent on the recruitment of immune cells, particularly granulocytes, into the skin. During an acute flare of disease, inflammatory skin lesions typically progressing from erythema through urticarial plaques to subepidermal blisters erosions erupt and, finally, completely resolve, thus illustrating that resolution of inflammation is continuously executed in pemphigoid disease patients and can be directly monitored on the skin. Despite these superb conditions for examining resolution in pemphigoid diseases as paradigm diseases for antibody-induced tissue inflammation, the mechanisms of resolution in pemphigoid are underinvestigated and still largely elusive. In the last decade, mouse models for pemphigoid diseases were developed, which have been instrumental to identify several key pathways for the initiation of inflammation in these diseases. More recently, also protective pathways, specifically IL-10 and C5aR2 signalling on the molecular level and T on the cellular level, counteracting skin inflammation have been highlighted and may contribute to the continuous execution of resolution in pemphigoid diseases. The upstream orchestrators of this process are currently under investigation. Pemphigoid disease patients, particularly bullous pemphigoid patients, who are predominantly above 75 years of age, often succumb to the side effects of the immunosuppressive therapeutics nowadays still required to suppress the disease. Pemphigoid disease patients may therefore represent a group of patients benefiting most substantially from the introduction of non-immunosuppressive, proresolving therapeutics into the treatment regimens for their disease.
Topics: Animals; Autoimmunity; Biomarkers; Disease Management; Disease Susceptibility; Epidermis; Humans; Inflammation Mediators; Lipid Metabolism; Pemphigoid, Bullous; Skin
PubMed: 31732776
DOI: 10.1007/s00281-019-00759-y -
Biochimica Et Biophysica Acta Feb 2013The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and... (Review)
Review
BACKGROUND
The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue.
SCOPE OF REVIEW
A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer.
MAJOR CONCLUSIONS
An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis.
GENERAL SIGNIFICANCE
Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells.
Topics: Epidermal Cells; Epidermis; Humans; Stem Cells
PubMed: 22820019
DOI: 10.1016/j.bbagen.2012.07.002 -
Journal of Endocrinological... Feb 2023This review will discuss the role of vitamin D and calcium signaling in the epidermal wound response with particular focus on the stem cells of the epidermis and hair... (Review)
Review
PURPOSE
This review will discuss the role of vitamin D and calcium signaling in the epidermal wound response with particular focus on the stem cells of the epidermis and hair follicle that contribute to the wounding response.
METHODS
Selected publications relevant to the mechanisms of wound healing in general and the roles of calcium and vitamin D in wound healing in particular were reviewed.
RESULTS
Following wounding the stem cells of the hair follicle and interfollicular epidermis are activated to proliferate and migrate to the wound where they take on an epidermal fate to re-epithelialize the wound and regenerate the epidermis. The vitamin D and calcium sensing receptors (VDR and CaSR, respectively) are expressed in the stem cells of the hair follicle and epidermis where they play a critical role in enabling the stem cells to respond to wounding. Deletion of Vdr and/or Casr from these cells delays wound healing. The VDR is regulated by co-regulators such as the Med 1 complex and other transcription factors such as Ctnnb (beta-catenin) and p63. The formation of the Cdh1/Ctnn (E-cadherin/catenin) complex jointly stimulated by vitamin D and calcium plays a critical role in the activation, migration, and re-epithelialization processes.
CONCLUSION
Vitamin D and calcium signaling are critical for the ability of epidermal and hair follicle stem cells to respond to wounding. Vitamin D deficiency with the accompanying decrease in calcium signaling can result in delayed and/or chronic wounds, a major cause of morbidity, loss of productivity, and medical expense.
Topics: Humans; Vitamin D; Calcium; Calcium Signaling; Epidermis; Wound Healing; Vitamins
PubMed: 35963983
DOI: 10.1007/s40618-022-01893-5 -
Skin Pharmacology and Physiology 2022The process by which drugs leave the bloodstream to enter the skin compartments is important in determining appropriate routes of delivery and developing more... (Review)
Review
BACKGROUND
The process by which drugs leave the bloodstream to enter the skin compartments is important in determining appropriate routes of delivery and developing more efficacious medications. We conducted a general literature review on percutaneous egression mechanisms.
SUMMARY
Studies demonstrate that the stratum corneum (SC) is a compartment for systemically delivered drugs. Upon reviewing the available literature, it became apparent that there may be multiple mechanisms of percutaneous egression dependent upon drug physiochemical properties. These mechanisms include, but are not limited to, desquamation, sebum secretion, sweat transport, and passive diffusion. While drugs often utilize one major pathway, it is possible that all mechanisms may play a role to varying extents.
KEY MESSAGES
Available literature suggests that hydrophilic substances tended to travel from blood to the upper layers of the skin via sweat, whereas lipophilic substances utilized sebum secretion to reach the SC. Upon reaching the skin surface, the drugs spread laterally before penetrating back into the skin as if they were topically administered. More data are warranted to identify additional percutaneous egression mechanisms, precise drug action sites, and accelerate drug development.
Topics: Diffusion; Epidermis
PubMed: 35325893
DOI: 10.1159/000523795 -
Frontiers in Immunology 2021The skin protects the human body against dehydration and harmful challenges. Keratinocytes (KCs) are the most abundant epidermal cells, and it is anticipated that...
The skin protects the human body against dehydration and harmful challenges. Keratinocytes (KCs) are the most abundant epidermal cells, and it is anticipated that KC-mediated transport of Na ions creates a physiological barrier of high osmolality against the external environment. Here, we studied the role of NFAT5, a transcription factor whose activity is controlled by osmotic stress in KCs. Cultured KCs from adult mice were found to secrete more than 300 proteins, and upon NFAT5 ablation, the secretion of several matrix proteinases, including metalloproteinase-3 (Mmp3) and kallikrein-related peptidase 7 (Klk7), was markedly enhanced. An increase in Mmp3 and Klk7 RNA levels was also detected in transcriptomes of KCs, along with increases of numerous members of the 'Epidermal Differentiation Complex' (EDC), such as small proline-rich (Sprr) and S100 proteins. NFAT5 and Mmp3 as well as NFAT5 and Klk7 are co-expressed in the basal KCs of fetal and adult epidermis but not in basal KCs of newborn (NB) mice. The poor NFAT5 expression in NB KCs is correlated with a strong increase in Mmp3 and Klk7 expression in KCs of NB mice. These data suggests that, along with the fragile epidermis of adult mice, NFAT5 keeps in check the expression of matrix proteases in epidermis. The NFAT5-mediated control of matrix proteases in epidermis contributes to the manifold changes in skin development in embryos before and during birth, and to the integrity of epidermis in adults.
Topics: Animals; Cell Differentiation; Epidermis; Keratinocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; NFATC Transcription Factors
PubMed: 34956208
DOI: 10.3389/fimmu.2021.780727