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Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer of the skin are sometimes referred to as basal keratinocytes. Keratinocytes form a barrier against environmental damage by heat, UV radiation, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually being shed, which happens every 40 to 56 days in humans.
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water released from the body into the atmosphere through transepidermal water loss.
Keratin 1 is a Type II intermediate filament (IFs) of the intracytoplasmatic cytoskeleton. Is co-expressed with and binds to Keratin 10, a Type I keratin, to form a coiled coil heterotypic keratin chain. Keratin 1 and Keratin 10 are specifically expressed in the spinous and granular layers of the epidermis. In contrast, basal layer keratinocytes express little to no Keratin 1. Mutations in KRT1, the gene encoding Keratin 1, have been associated with variants of the disease bullous congenital ichthyosiform erythroderma in which the palms and soles of the feet are affected. Mutations in KRT10 have also been associated with bullous congenital ichthyosiform erythroderma; however, in patients with KRT10 mutations the palms and soles are spared. This difference is likely due to Keratin 9, rather than Keratin 10, being the major binding partner of Keratin 1 in acral keratinocytes.
Hyaluronic acid, also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans as it is non-sulfated, forms in the plasma membrane instead of the Golgi apparatus, and can be very large: human synovial HA averages about 7 MDa per molecule, or about 20,000 disaccharide monomers, while other sources mention 3–4 MDa.
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their function lead to a range of developmental defects. These growth factors typically act as systemic or locally circulating molecules of extracellular origin that activate cell surface receptors. A defining property of FGFs is that they bind to heparin and to heparan sulfate. Thus, some are sequestered in the extracellular matrix of tissues that contains heparan sulfate proteoglycans and are released locally upon injury or tissue remodeling.
Desmoglein-3 is a protein that in humans is encoded by the DSG3 gene. In the skin epidermis Desmoglein-3 is expressed in the basal lower layers of the epidermis, and dominates in terms of expression on mucosal surfaces compared to Desmoglein-1.
Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol, which is sphingosine.
Tacalcitol (1,24-dihydroxyvitamin D3) is a synthetic vitamin D3 analog. Tacalcitol is marketed under several names, including Curatoderm and Bonalfa.
Corneocytes are terminally differentiated keratinocytes and compose most of the stratum corneum, the outermost layer of the epidermis. They are regularly replaced through desquamation and renewal from lower epidermal layers and are essential for its function as a skin barrier.
S100 calcium-binding protein A2 (S100A2) is a protein that in humans is encoded by the S100A2 gene and it is located on chromosome 1q21 with other S100 proteins.
Dystonin(DST), also known as bullous pemphigoid antigen 1 (BPAG1), isoforms 1/2/3/4/5/8, is a protein that in humans is encoded by the DST gene.
Calcium-transporting ATPase type 2C member 1 is an enzyme that in humans is encoded by the ATP2C1 gene.
Cytochrome P450 family 24 subfamily A member 1 (abbreviated CYP24A1) is a member of the cytochrome P450 superfamily of enzymes encoded by the CYP24A1 gene. It is a mitochondrial monooxygenase which catalyzes reactions including 24-hydroxylation of calcitriol (1,25-dihydroxyvitamin D3). It has also been identified as vitamin D3 24-hydroxylase.(EC 1.14.15.16)
Thioredoxin-interacting protein is a protein that in humans is encoded by the TXNIP gene.
Fatty acid-binding protein, epidermal is a protein that in humans is encoded by the FABP5 gene.
Fibroblast growth factor 5 is a protein that in humans is encoded by the FGF5 gene.
Caspase 14 is an enzyme that in humans is encoded by the CASP14 gene. Orthologs of this gene also exist in other mammals, such as sirenians and cetaceans, though they are inactivated in these two clades. Curiously, manatees, which are sirenians, retain some functional CASP14 genes.
Secreted Ly-6/uPAR-related protein 1 is a protein that in humans is encoded by the SLURP1 gene. It exerts anti-inflammatory effects, acts as a tumor suppressor, and antagonizes nicotinic receptors.
Keratin, type I cuticular Ha1 is a protein that in humans is encoded by the KRT31 gene.
Michael F. Holick is an American adult endocrinologist, specializing in vitamin D, such as the identification of both calcidiol, the major circulating form of vitamin D, and calcitriol, the active form of vitamin D. His work has been the basis for diagnostic tests and therapies for vitamin D-related diseases. He is a professor of medicine at the Boston University Medical Center and editor-in-chief of the journal Clinical Laboratory.
References
- ↑ Boukamp, Petra; Petrussevska, Rule T.; Breitkreutz, Dirk; Hornung, Jiirgen; Markham, Alex; Fusenig, Norbert E. (1 March 1988). "Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line". The Journal of Cell Biology. 106 (3): 761–771. doi:10.1083/jcb.106.3.761. PMC 2115116 . PMID 2450098.
- ↑ Ölschläger, Veronika; Schrader, Andreas; Hockertz, Stefan (13 December 2011). "Comparison of Primary Human Fibroblasts and Keratinocytes with Immortalized Cell Lines Regarding their Sensitivity to Sodium Dodecyl Sulfate in a Neutral Red Uptake Cytotoxicity Assay". Arzneimittelforschung. 59 (3): 146–152. doi:10.1055/s-0031-1296378. PMID 19402346. S2CID 20840726.
- ↑ Schoop, Veronika M.; Fusenig, Norbert E.; Mirancea, Nicolae (March 1999). "Epidermal Organization and Differentiation of HaCaT Keratinocytes in Organotypic Coculture with Human Dermal Fibroblasts". Journal of Investigative Dermatology. 112 (3): 343–353. doi: 10.1046/j.1523-1747.1999.00524.x . PMID 10084313.
- ↑ Schürer, N; Köhne, A; Schliep, V; Barlag, K; Goerz, G (Aug 1993). "Lipid composition and synthesis of HaCaT cells, an immortalized human keratinocyte line, in comparison with normal human adult keratinocytes". Experimental Dermatology. 2 (4): 179–85. doi:10.1111/j.1600-0625.1993.tb00030.x. PMID 8162337. S2CID 20709063.
- ↑ Lehmann, Bodo (1 January 1997). "HaCaT Cell Line as a Model System for Vitamin D3 Metabolism in Human Skin". Journal of Investigative Dermatology. 108 (1): 78–82. doi: 10.1111/1523-1747.ep12285640 . PMID 8980292.