Function Of Epidermal Cells Research Articles

Synergistic effect of cerium chloride and calcium chloride alters calcium signaling in keratinocytes to promote epidermal differentiation.

Epidermal keratinocytes undergo morphological and functional changes during differentiation, eventually being enucleated to become corneocytes. Calcium has been shown to be involved in various cellular functions of epidermal cells, including proliferation, differentiation, and apoptosis. Cerium is a lanthanide-series element and rare earth metal. For skin, cerium oxide has been investigated for use in absorbing UV and promoting wound healing. However, the functions and physiological effects of inorganic cerium on the skin have rarely been investigated. Here, we focused on cerium's function in epidermal keratinocytes and its interaction with calcium by investigating their effects on cell differentiation and intracellular calcium concentration. This study showed that applying cerium chloride to epidermal keratinocytes altered calcium signaling. It also suggested that cerium and calcium induced an increase in intracellular calcium concentration and promoted keratinocyte differentiation.

Impact of Skin Exposure to Benzo[a]pyrene in Rat Model: Insights into Epidermal Cell Function and Draining Lymph Node Cell Response.

The skin is a direct target of the air pollutant benzo[a]pyrene (BaP). While its carcinogenic qualities are well-studied, the immunotoxicity of BaP after dermal exposure is less understood. This study examines the immunomodulatory effects of a 10-day epicutaneous BaP application, in environmentally/occupationally relevant doses, by analyzing ex vivo skin immune response (skin explant, epidermal cells and draining lymph node/DLN cell activity), alongside the skin's reaction to sensitization with experimental hapten dinitrochlorobenzene (DNCB). The results show that BaP application disrupts the structure of the epidermal layer and promotes immune cell infiltration in the dermis. BaP exposure led to oxidative stress in epidermal cells, characterized by decreased reduced glutathione and increased AHR and Cyp1A1 expression. Production and gene expression of proinflammatory cytokines (TNF, IL-1β) by epidermal cells decreased, while IL-10 response increased. Decreased spontaneous production of IFN-γ and IL-17, along with unchanged IL-10, was observed in DLC cells, whereas ConA-stimulated production of these cytokines was elevated. Local immunosuppression caused by BaP application seems to reduce the skin's response to an additional stimulus, evidenced by decreased effector activity of DLN cells three days after sensitization with DNCB. These findings provide new insight into the immunomodulatory effects and health risks associated with skin exposure to BaP.

Improving dermal fibroblast-to-epidermis communications and aging wound repair through extracellular vesicle-mediated delivery of Gstm2 mRNA

Skin aging is characterized by the disruption of skin homeostasis and impaired skin injury repair. Treatment of aging skin has long been limited by the unclear intervention targets and delivery techniques. Engineering extracellular vesicles (EVs) as an upgraded version of natural EVs holds great potential in regenerative medicine. In this study, we found that the expression of the critical antioxidant and detoxification gene Gstm2 was significantly reduced in aging skin. Thus, we constructed the skin primary fibroblasts-derived EVs encapsulating Gstm2 mRNA (EVsGstm2), and found that EVsGstm2 could significantly improve skin homeostasis and accelerate wound healing in aged mice. Mechanistically, we found that EVsGstm2 alleviated oxidative stress damage of aging dermal fibroblasts by modulating mitochondrial oxidative phosphorylation, and promoted dermal fibroblasts to regulate skin epidermal cell function by paracrine secretion of Nascent Polypeptide-Associated Complex Alpha subunit (NACA). Furthermore, we confirmed that NACA is a novel skin epidermal cell protective molecule that regulates skin epidermal cell turnover through the ROS-ERK-ETS-Cyclin D pathway. Our findings demonstrate the feasibility and efficacy of EVs-mediated delivery of Gstm2 for aged skin treatment and unveil novel roles of GSTM2 and NACA for improving aging skin.Graphical

Adipose mesenchymal stem cell-derived exosomes promote skin wound healing in diabetic mice by regulating epidermal autophagy.

Adipose mesenchymal stem cell-derived exosomes (ADSC-Exos) have great potential in the field of tissue repair and regenerative medicine, particularly in cases of refractory diabetic wounds. Interestingly, autophagy plays a role in wound healing, and recent research has demonstrated that exosomes are closely associated with intracellular autophagy in biogenesis and molecular signaling mechanisms. Therefore, this study aimed to investigate whether ADSC-Exos promote the repair of diabetic wounds by regulating autophagy to provide a new method and theoretical basis for the treatment of diabetic wounds. Western blot analysis and autophagy double-labelled adenovirus were used to monitor changes in autophagy flow in human immortalized keratinocyte cell line (HaCaT) cells. ADSC-Exos were generated from ADSC supernatants via ultracentrifugation. The effectiveness of ADSC-Exos on HaCaT cells was assessed using a live-cell imaging system, cell counting kit-8 and cell scratch assays. The cells were treated with the autophagy inhibitor bafilomycin A1 to evaluate the effects of autophagy on cell function. The recovery of diabetic wounds after ADSC-Exo treatment was determined by calculating the healing rates and performing histological analysis. High-throughput transcriptome sequencing was used to analyze changes in mRNA expression after the treatment of HaCaT cells with ADSC-Exos. ADSC-Exos activated autophagy in HaCaT cells, which was inhibited by high glucose levels, and potentiated their cellular functions. Moreover, ADSC-Exos in combination with the autophagy inhibitor bafilomycin A1 showed that autophagy defects further impaired the biological function of epidermal cells under high-glucose conditions and partially weakened the healing effect of ADSC-Exos. Using a diabetes wound model, we found that ADSC-Exos promoted skin wound healing in diabetic mice, as evidenced by increased epidermal autophagy and rapid re-epithelialization. Finally, sequencing results showed that increased expression of autophagy-related genes nicotinamide phosphoribosyltransferase (NAMPT), CD46, vesicle-associated membrane protein 7 (VAMP7), VAMP3 and eukaryotic translation initiation factor 2 subunit alpha (EIF2S1) may contribute to the underlying mechanism of ADSC-Exo action. This study elucidated the molecular mechanism through which ADCS-Exos regulate autophagy in skin epithelial cells, thereby providing a new theoretical basis for the treatment and repair of skin epithelial damage by ADSC-Exos.

Expression and possible functions of a horizontally transferred glycosyl hydrolase gene, GH6-1, in Ciona embryogenesis

BackgroundThe Tunicata or Urochordata is the only animal group with the ability to synthesize cellulose directly and cellulose is a component of the tunic that covers the entire tunicate body. The genome of Ciona intestinalis type A contains a cellulose synthase gene, CesA, that it acquired via an ancient, horizontal gene transfer. CesA is expressed in embryonic epidermal cells and functions in cellulose production. Ciona CesA is composed of both a glycosyltransferase domain, GT2, and a glycosyl hydrolase domain, GH6, which shows a mutation at a key position and seems functionless. Interestingly, the Ciona genome contains a glycosyl hydrolase gene, GH6-1, in which the GH6 domain seems intact. This suggests expression and possible functions of GH6-1 during Ciona embryogenesis. Is GH6-1 expressed during embryogenesis? If so, in what tissues is the gene expressed? Does GH6-1 serve a function? If so, what is it? Answers to these questions may advance our understanding of evolution of this unique animal group.ResultsQuantitative reverse transcription PCR and in situ hybridization revealed that GH6-1 is expressed in epidermis of tailbud embryos and in early swimming larvae, a pattern similar to that of CesA. Expression is downregulated at later stages and becomes undetectable in metamorphosed juveniles. The GH6-1 expression level is higher in the anterior-trunk region and caudal-tip regions of late embryos. Single-cell RNA sequencing analysis of the late tailbud stage showed that cells of three clusters with epidermal identity express GH6-1, and that some of them co-express CesA. TALEN-mediated genome editing was used to generate GH6-1 knockout Ciona larvae. Around half of TALEN-electroporated larvae showed abnormal development of adhesive papillae and altered distribution of surface cellulose. In addition, three-fourths of TALEN-electroporated animals failed to complete larval metamorphosis.ConclusionsThis study showed that tunicate GH6-1, a gene that originated by horizontal gene transfer of a prokaryote gene, is recruited into the ascidian genome, and that it is expressed and functions in epidermal cells of ascidian embryos. Although further research is required, this observation demonstrates that both CesA and GH6-1 are involved in tunicate cellulose metabolism, impacting tunicate morphology and ecology.

Exosomal microRNAs from Mesenchymal Stem Cells: Novel Therapeutic Effect in Wound Healing.

Wound healing is a complicated biological process that leads to the regeneration of damaged skin tissue. Determining the methods to promote wound healing has become a hot topic in medical cosmetology and tissue repair research. Mesenchymal stem cells (MSCs) are a group of stem cells with the potential of self-renewal and multi-differentiation. MSCs transplantation has a broad application prospect in wound healing therapy. Many studies have demonstrated that the therapeutic capacity of MSCs is mainly mediated by paracrine actions. Exosomes (EXOs), which are nanosized vesicles carrying a variety of nucleic acids, proteins and lipids, are an important component of paracrine secretion. It has been demonstrated that exosomal microRNAs (EXO-miRNAs) play a key role in the function of exosomes. In this review, we focus on current research on miRNAs from MSC-derived exosomes (MSC-EXO miRNAs) in terms of sorting, releasing and function and their effects on inflammation regulation, epidermal cell function, fibroblast function, and extracellular matrix formation. At last, we discuss the current attempts to improve the treatment of MSC-EXO-miRNAs. Many studies have demonstrated that MSC-EXO miRNAs play a key role in promoting wound healing. They have been shown to regulate inflammation response, enhance epidermal cell proliferation and migration, stimulate fibroblast proliferation and collagen synthesis, and regulate extracellular matrix formation. Besides, there have been a number of strategies developed to promote MSC-EXO and MSC-EXO miRNAs for wound healing treatment. Utilizing the association of exosomes from MSCs with miRNAs may be a promising strategy to promote trauma healing. MSC-EXO miRNAs may provide a new approach to promote wound healing and improve the quality of life for patients with skin injuries.

Stem Cell-Derived Exosomes: A New Method for Reversing Skin Aging.

Senescence is an inevitable natural life process that involves structural and functional degeneration of tissues and organs. Recently, the process of skin aging has attracted much attention. Determining a means to delay or even reverse skin aging has become a research hotspot in medical cosmetology and anti-aging. Dysfunction in the epidermis and fibroblasts and changes in the composition and content of the extracellular matrix are common pathophysiological manifestations of skin aging. Reactive oxygen species and matrix metalloproteinases play essential roles in this process. Stem cells are pluripotent cells that possess self-replication abilities and can differentiate into multiple functional cells under certain conditions. These cells also possess a strong ability to facilitate tissue repair and regeneration. Stem cell transplantation has the potential for application in anti-aging therapy. Increasing studies have demonstrated that stem cells perform functions through paracrine processes, particularly those involving exosomes. Exosomes are nano-vesicular substances secreted by stem cells that participate in cell-to-cell communication by transporting their contents into target cells. In this chapter, the biological characteristics of exosomes were reviewed, including their effects on extracellular matrix formation, epidermal cell function, fibroblast function and antioxidation. Exosomes derived from stem cells may provide a new means to reverse skin aging.

Role of skin immunity on wound healing

The immune system of skin is consisted of different types of immune cells which distribute in epidermis and dermis. By adjusting the microenvironment of wound, these immune cells regulate the migration, proliferation, differentiation and other functions of epidermal cells, endothelial cells, and fibroblasts, thus taking part in re-epithelialization and formation of granulation tissue and having great influences on wound healing in the end. Acknowledging the interaction of these cells and identifying the targets that regulate the functions of immune cells will provide direction for improving the speed and quality of wound healing.

Mapping and Dynamics of Regulatory DNA in Maturing Arabidopsis thaliana Siliques.

The genome is reprogrammed during development to produce diverse cell types, largely through altered expression and activity of key transcription factors. The accessibility and critical functions of epidermal cells have made them a model for connecting transcriptional events to development in a range of model systems. In Arabidopsis thaliana and many other plants, fertilization triggers differentiation of specialized epidermal seed coat cells that have a unique morphology caused by large extracellular deposits of polysaccharides. Here, we used DNase I-seq to generate regulatory landscapes of A. thaliana seeds at two critical time points in seed coat maturation (4 and 7 DPA), enriching for seed coat cells with the INTACT method. We found over 3,000 developmentally dynamic regulatory DNA elements and explored their relationship with nearby gene expression. The dynamic regulatory elements were enriched for motifs for several transcription factors families; most notably the TCP family at the earlier time point and the MYB family at the later one. To assess the extent to which the observed regulatory sites in seeds added to previously known regulatory sites in A. thaliana, we compared our data to 11 other data sets generated with 7-day-old seedlings for diverse tissues and conditions. Surprisingly, over a quarter of the regulatory, i.e. accessible, bases observed in seeds were novel. Notably, plant regulatory landscapes from different tissues, cell types, or developmental stages were more dynamic than those generated from bulk tissue in response to environmental perturbations, highlighting the importance of extending studies of regulatory DNA to single tissues and cell types during development.

Spironolactone Depletes the XPB Protein and Inhibits DNA Damage Responses in UVB-Irradiated Human Skin

UVB wavelengths of light induce the formation of photoproducts in genomic DNA that are potentially mutagenic and detrimental to epidermal cell function. The mineralocorticoid and androgen receptor antagonist spironolactone (SP) was recently identified as an inhibitor of UV photoproduct removal in human cancer cells invitro via its ability to promote the rapid proteolytic degradation of the DNA repair protein XPB. Using normal human keratinocytes invitro and skin explants exvivo, we found that SP rapidly depleted XPB protein in both systems and abrogated two major responses to UVB-induced DNA damage, including the removal of UV photoproducts from genomic DNA and the activation of ATR/ATM DNA damage kinase signaling. These effects were also correlated with both mutagenesis and a predisposition to UVB-induced cell death but were unique to SP, because neither the SP metabolites canrenone and 7α-thiomethylspironolactone nor the more specific mineralocorticoid receptor antagonist eplerenone affected XPB protein levels or the UVB response. Our findings provide an approach for studying XPB and its roles in the UVB DNA damage response in human skin exvivo and indicate that SP may increase UVB mutagenesis and skin cancer risk in certain individuals.

Amino Carbonylation of Epidermal Basement Membrane Inhibits Epidermal Cell Function and Is Suppressed by Methylparaben

This study investigated the effect of amino carbonylation (Maillard reaction) on the function of the epidermal basement membrane (BM) by analyzing epidermal cell proliferation and keratinization and stratum corneum barrier function using a three-dimensional human epidermal BM model treated with glyceraldehyde. Intracellular ATP levels were lower in cells cultured on amino-carbonylated epidermal BM as compared to those in normal epidermal BM (control). Moreover, trans-epidermal water loss was increased by culturing on amino-carbonylated BM relative to the control; this was accompanied by downregulation of filaggrin, transglutaminase-1, and serine palmitoyltransferase 2 mRNA levels. p-Hydroxybenzoic acid methyl ester (methylparaben) abrogated the decrease in ATP production and filaggrin expression in human keratinocytes induced by amino-carbonylated collagen. Thus, amino carbonylation of the epidermal BM inhibits moisture retention, keratinization, and ceramide synthesis and disrupts the barrier function of the stratum corneum. These findings suggest that methylparaben can be an effective additive to cosmetics for improving epidermal function that is compromised by amino carbonylation.

Fabrication of PLA/Ag nanofibers by green synthesis method using Momordica charantia fruit extract for wound dressing applications

The paper outlines the antibacterial, in-vitro biocompatibility assay, and mechanical properties of PLA/Ag nanofibers fabricated by electrospinning technique. The colloidal nanosilver involved in the system were synthesized using biological reduction method from silver nitrate (AgNO3) and bitter gourd extract (reducing agent) in diphase medium containing PLA matrix (capping agent). The nanofibers were characterized using Scanning electron microscopy (SEM), Transmission electron microscope (TEM), Energy dispersive X-ray spectroscopy (EDS), Dynamic light scattering technique (DLS), Fourier transform-infrared spectroscopy (AT-IR), X-ray diffraction (XRD), Contact angle (WCs), Fluorescence spectroscopy and UV–vis spectroscopy (UV–vis). The capping agent (PLA) interaction with colloidal nanosilver was confirmed by the X-ray photoelectron spectroscopy (XPS). Appreciable antibacterial property was observed for PLA/Ag nanofibers on screening it against Escherichia coli and Staphylococcus aureus by agar disc diffusion method. The spherical particles with an average size of about 5–20nm were deduced by Transmission electron microscopy (TEM) analysis. The in-vitro analysis showed that the biofabricated PLA/Ag nanofiber (with Hemolytic percentage less than 5%) were also cytocompatible with fibroblast cell and does not impair cell growth. An observed WVTR of 2237.53±165g/m2.24h seem to provide an optimal moist environment locally to promote wound healing. All these results justify PLA/Ag nanofibers as a wound healer that can enhance the proliferation and function of epidermal cells and fibroblasts.

Rictor/mTORC2 deficiency enhances keratinocyte stress tolerance via mitohormesis.

How metabolic pathways required for epidermal tissue growth and remodeling influence the ability of keratinocytes to survive stressful conditions is still largely unknown. The mechanistic target of rapamycin complex 2 (mTORC2) regulates growth and metabolism of several tissues, but its functions in epidermal cells are poorly defined. Rictor is an adaptor protein essential for mTORC2 activity. To explore the roles of mTORC2 in the epidermis, we have conditionally deleted rictor in mice via K14-Cre-mediated homologous recombination and found that its deficiency causes moderate tissue hypoplasia, reduced keratinocyte proliferation and attenuated hyperplastic response to TPA. Noteworthy, rictor-deficient keratinocytes displayed increased lifespan, protection from senescence, and enhanced tolerance to cellular stressors such as growth factors deprivation, epirubicin and X-ray in vitro and radioresistance in vivo. Rictor-deficient keratinocytes exhibited changes in global gene expression profiles consistent with metabolic alterations and enhanced stress tolerance, a shift in cell catabolic processes from glycids and lipids to glutamine consumption and increased production of mitochondrial reactive oxygen species (ROS). Mechanistically, the resiliency of rictor-deficient epidermal cells relies on these ROS increases, indicating stress resistance via mitohormesis. Thus, our findings reveal a new link between metabolic changes and stress adaptation of keratinocytes centered on mTORC2 activity, with potential implications in skin aging and therapeutic resistance of epithelial tumors.

Controlled water vapor transmission rate promotes wound-healing via wound re-epithelialization and contraction enhancement.

A desirable microenvironment is essential for wound healing, in which an ideal moisture content is one of the most important factors. The fundamental function and requirement for wound dressings is to keep the wound at an optimal moisture. Here, we prepared serial polyurethane (PU) membrane dressings with graded water vapor transmission rates (WVTRs), and the optimal WVTR of the dressing for wound healing was identified by both in vitro and in vivo studies. It was found that the dressing with a WVTR of 2028.3 ± 237.8 g/m2·24 h was able to maintain an optimal moisture content for the proliferation and regular function of epidermal cells and fibroblasts in a three-dimensional culture model. Moreover, the dressing with this optimal WTVR was found to be able to promote wound healing in a mouse skin wound model. Our finds may be helpful in the design of wound dressing for wound regeneration in the future.

Lgr4 Promotes Glioma Cell Proliferation through Activation of Wnt Signaling

The key signaling networks regulating glioma cell proliferation remain poorly defined. The leucine-rich repeat containing G-protein coupled receptor 4 (Lgr4) has been implicated in intestinal, gastric, and epidermal cell functions. We investigated whether Lgr4 functions in glioma cells and found that Lgr4 expression was significantly increased in glioma tissues. In addition, Lgr4 overexpression promoted while its knockdown using small interfering RNA oligos inhibited glioma cell proliferation. In addition, Wnt/β-catenin signaling was activated in cells overexpressing Lgr4. Therefore, our results revealed that Lgr4 activates Wnt/β-catenin signaling to regulate glioma cell proliferation.

Gene expression patterns specific to the regenerating limb of the Mexican axolotl

SummarySalamander limb regeneration is dependent upon tissue interactions that are local to the amputation site. Communication among limb epidermis, peripheral nerves, and mesenchyme coordinate cell migration, cell proliferation, and tissue patterning to generate a blastema, which will form missing limb structures. An outstanding question is how cross-talk between these tissues gives rise to the regeneration blastema. To identify genes associated with epidermis-nerve-mesenchymal interactions during limb regeneration, we examined histological and transcriptional changes during the first week following injury in the wound epidermis and subjacent cells between three injury types; 1) a flank wound on the side of the animal that will not regenerate a limb, 2) a denervated limb that will not regenerate a limb, and 3) an innervated limb that will regenerate a limb. Early, histological and transcriptional changes were similar between the injury types, presumably because a common wound-healing program is employed across anatomical locations. However, some transcripts were enriched in limbs compared to the flank and are associated with vertebrate limb development. Many of these genes were activated before blastema outgrowth and expressed in specific tissue types including the epidermis, peripheral nerve, and mesenchyme. We also identified a relatively small group of transcripts that were more highly expressed in innervated limbs versus denervated limbs. These transcripts encode for proteins involved in myelination of peripheral nerves, epidermal cell function, and proliferation of mesenchymal cells. Overall, our study identifies limb-specific and nerve-dependent genes that are upstream of regenerative growth, and thus promising candidates for the regulation of blastema formation.

Pleiotropic phenotypes of the sticky peel mutant provide new insight into the role of CUTIN DEFICIENT2 in epidermal cell function in tomato.

Plant epidermal cells have evolved specialist functions associated with adaptation to stress. These include the synthesis and deposition of specialized metabolites such as waxes and cutin together with flavonoids and anthocyanins, which have important roles in providing a barrier to water loss and protection against UV radiation, respectively. Characterization of the sticky peel (pe) mutant of tomato (Solanum lycopersicum) revealed several phenotypes indicative of a defect in epidermal cell function, including reduced anthocyanin accumulation, a lower density of glandular trichomes, and an associated reduction in trichome-derived terpenes. In addition, pe mutant fruit are glossy and peels have increased elasticity due to a severe reduction in cutin biosynthesis and altered wax deposition. Leaves of the pe mutant are also cutin deficient and the epicuticular waxes contain a lower proportion of long-chain alkanes. Direct measurements of transpiration, together with chlorophyll-leaching assays, indicate increased cuticular permeability of pe leaves. Genetic mapping revealed that the pe locus represents a new allele of CUTIN DEFICIENT2 (CD2), a member of the class IV homeodomain-leucine zipper gene family, previously only associated with cutin deficiency in tomato fruit. CD2 is preferentially expressed in epidermal cells of tomato stems and is a homolog of Arabidopsis (Arabidopsis thaliana) ANTHOCYANINLESS2 (ANL2). Analysis of cuticle composition in leaves of anl2 revealed that cutin accumulates to approximately 60% of the levels observed in wild-type Arabidopsis. Together, these data provide new insight into the role of CD2 and ANL2 in regulating diverse metabolic pathways and in particular, those associated with epidermal cells.

Phosphate deficiency-induced cell wall remodeling

The formation of root hairs is a unique developmental process that requires the concerted action of a multitude of proteins. Root hair development is controlled by intrinsic programs, but fine-tuning of these programs occurs in response to environmental signals, dictating the shape and function of epidermal cells. In particular, low availability of soil-immobile mineral nutrients such as phosphate (Pi) affects the density and length of root hairs, resulting in an increased absorptive surface area. We recently reported on a time-course transcriptional profiling study aimed at identifying gene networks that signal Pi deficiency and mediate adaptation to Pi shortage. Using root-specific coexpression analysis of early Pi-responsive genes, we identified a subset of novel loci crucial for the development of root hairs under Pi-deficient conditions. Remodeling of cell wall structures may be associated with the TOR (Target of Rapamycin) pathway, a highly conserved central regulator of growth and development in eukaryotic cells that senses nutrient availability.

Fundamental hair follicle biology and fine fibre production in animals

Hair ‘fine’ fibre is an important commercial product of farmed and certain wild animal species. The fibre is produced in follicles embedded in skin. These have properties in common with other tissues of the integument and have importance in determining yield and quality of fibre. Means of understanding and improving these characteristics are informed by knowledge of integumental and follicle biology. This paper reviews contemporary information that identifies the major fibre-producing species and their production characteristic. It surveys knowledge describing fundamental biology of the integument and considers information derived for the hair follicle from studies on a number of species including genetically modified mice. It identifies the composition of the follicle and describes components and interrelationships between epidermal hair-fibre producing epidermis and fibroblast- and connective tissue-containing dermis. The structure of different primary and secondary follicle types, and associated structures, are described. Focus is given to the alterations in anatomy and in behaviour from active to inactive state, which occurs during the hair follicle cycle. Information is provided on the anatomical substructures (hair medulla, cortex, cuticles and supporting sheaths and dermal papilla), cellular and extracellular composition, and adhesion and chemical signalling systems, which regulate development from the early embryo to post-natal state and subsequent cycling. Such signalling involves the dermis and its specialist fibroblasts, which secrete signalling molecules, which along with those from local epidermis and systemic sources, largely determine structure and function of epidermal cells. Such chemical signalling typically includes endocrine-, paracrine-, autocrine- and juxtacrine-acting molecules and interactions with their receptors located on cell membranes or intracellularly with transduction of message mediated by transcription factors at gene level. Important hormones and growth factors and inhibitors regulating morphogenic and/or mitogenic activity are identified. These mediate mechanisms associated with presence or absence in skin and development of patterning for primary or secondary follicles. Reference is made to deposition of individual keratins and keratin-associated proteins in follicle sub-structures and to fibre properties such as length, diameter, medullation, crimp and lustre. Pre- and post-natal regulation of pigmentation by melanocytes is reviewed. Brief attention is given to genomic and non-genomic variation and impact on the phenotypes expressed and the role of regulatory gene products as potential molecular markers for selection of superior animals. The importance of nutrients in providing substrates for follicular structures and enzymes and in molecules facilitating gene expression is also considered.

Tight junctions and tight junction proteins in mammalian epidermis

Tight junctions (TJ) are barrier forming cell–cell junctions that are found in a variety of cell types and tissues but their existence in mammalian epidermis has been shown only in the last years. A variety of TJ proteins were identified in mammalian epidermis, comprising several members of the claudin family, occludin, and JAM-A as well as ZO-1 and MUPP-1. TJ proteins exhibit complex expression and localization patterns in the epidermis. Nonetheless, even though several TJ proteins are found in various layers, typical TJ structures are only found in the stratum granulosum. TJ are important for barrier function of the skin, especially for inside–out barrier. In addition, TJ proteins might also be involved in additional functions in epidermal cells. Localization and expression of TJ proteins are altered in several skin diseases, e.g. psoriasis. Meanwhile several TJ modulators are known from simple epithelia. We discuss their putative usability for drug delivery into and through the skin.