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Keratohyalin is a protein structure found in cytoplasmic granules of the keratinocytes in the stratum granulosum of the epidermis. Keratohyalin granules (KHG) mainly consist of keratin, profilaggrin, [1] loricrin [2] and trichohyalin proteins which contribute to cornification or keratinization, the process of the formation of epidermal cornified cell envelope. During the keratinocyte differentiation, these granules maturate and expand in size, which leads to the conversion of keratin tonofilaments into a homogenous keratin matrix, an important step in cornification. [3]
Keratohyalin granules can be divided in three classes: globular KHG (found in quickly dividing epithelia, such as the oral mucose), stellate KHG (found in the slowly dividing normal epidermis) and KHG of Hassall's corpuscles or type VI epithelioreticular cells of the thymus gland. [4] The exact purpose of the keratinization of Hassall's corpuscles remains unknown.
During skin differentiation process, keratohyaline granules discharge their contents in the junction between stratum granulosum and stratum corneum cell layers and form the barrier. At the same time, the inner side of the cell membrane thickens forming the cornified cell envelope. After the release of the granules, nuclei, ribosomes and mitochondria disappear, the cells become densely packaged with filaggrin and cover more surface. After final dehydration, the cell desquamates. [5]
Keratohyalin granules contribute significantly to the process of skin moisturization, albeit indirectly. As keratinocytes differentiate and move towards the surface of the skin, they release keratohyalin granules, which contain filaggrin. Filaggrin is then chemically modified and proteolytically processed to form natural moisturizing factor (NMF). NMF is composed of hygroscopic (water-attracting) amino acids and derivatives, which help the stratum corneum, the outermost layer of the skin, to retain moisture. Additionally, NMF serves as a UV protectant and modulates the pH of the stratum corneum, both critical functions for skin health. [6] [7] [8]
The integumentary system is the set of organs forming the outermost layer of an animal's body. It comprises the skin and its appendages, which act as a physical barrier between the external environment and the internal environment that it serves to protect and maintain the body of the animal. Mainly it is the body's outer skin.
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.
The stratum corneum is the outermost layer of the epidermis. Consisting of dead tissue, it protects underlying tissue from infection, dehydration, chemicals and mechanical stress. It is composed of 15–20 layers of flattened cells with no nuclei and cell organelles.
Desquamation occurs when the outermost layer of a tissue, such as the skin, is shed. The term is from Latin desquamare 'to scrape the scales off a fish'.
Hyperkeratosis is thickening of the stratum corneum, often associated with the presence of an abnormal quantity of keratin, and is usually accompanied by an increase in the granular layer. As the corneum layer normally varies greatly in thickness in different sites, some experience is needed to assess minor degrees of hyperkeratosis.
The stratum lucidum is a thin, clear layer of dead skin cells in the epidermis named for its translucent appearance under a microscope. It is readily visible by light microscopy only in areas of thick skin, which are found on the palms of the hands and the soles of the feet.
The stratum granulosum is a thin layer of cells in the epidermis lying above the stratum spinosum and below the stratum corneum. Keratinocytes migrating from the underlying stratum spinosum become known as granular cells in this layer. These cells contain keratohyalin granules, which are filled with histidine- and cysteine-rich proteins that appear to bind the keratin filaments together. Therefore, the main function of keratohyalin granules is to bind intermediate keratin filaments together.
Filaggrin is a filament-associated protein that binds to keratin fibers in epithelial cells. Ten to twelve filaggrin units are post-translationally hydrolyzed from a large profilaggrin precursor protein during terminal differentiation of epidermal cells. In humans, profilaggrin is encoded by the FLG gene, which is part of the S100 fused-type protein (SFTP) family within the epidermal differentiation complex on chromosome 1q21. In cetaceans and sirenians, the FLG family has lost its function, with the curious exception of manatees in the latter clade: manatees still retain some functional FLG genes.
Spinous cells, or prickle cells, are keratin producing epidermal cells owing their prickly appearance to their numerous intracellular connections. They make up the stratum spinosum of the epidermis and provide a continuous net-like layer of protection for underlying tissue. They are susceptible to mutations caused by sunlight and can become malignant.
A stratified squamous epithelium consists of squamous (flattened) epithelial cells arranged in layers upon a basal membrane. Only one layer is in contact with the basement membrane; the other layers adhere to one another to maintain structural integrity. Although this epithelium is referred to as squamous, many cells within the layers may not be flattened; this is due to the convention of naming epithelia according to the cell type at the surface. In the deeper layers, the cells may be columnar or cuboidal. There are no intercellular spaces. This type of epithelium is well suited to areas in the body subject to constant abrasion, as the thickest layers can be sequentially sloughed off and replaced before the basement membrane is exposed. It forms the outermost layer of the skin and the inner lining of the mouth, esophagus and vagina.
In cell biology, lamellar bodies are secretory organelles found in type II alveolar cells in the lungs, and in keratinocytes in the skin. They are oblong structures, appearing about 300-400 nm in width and 100-150 nm in length in transmission electron microscopy images. Lamellar bodies in the alveoli of the lungs fuse with the cell membrane and release pulmonary surfactant into the extracellular space.
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.
Involucrin is a protein component of human skin and in humans is encoded by the IVL gene. In binding the protein loricrin, involucrin contributes to the formation of a cell envelope that protects corneocytes in the skin.
Loricrin is a protein that in humans is encoded by the LOR gene.
Skin sloughing is the process of shedding dead surface cells from the skin. It is most associated with cosmetic skin maintenance via exfoliation, but can also occur biologically or for medical reasons.
TGM5 is a transglutaminase enzyme.
Trichohyalin is a protein that in mammals is encoded by the TCHH gene.
The epidermal differentiation complex (EDC) is a gene complex comprising over fifty genes encoding proteins involved in the terminal differentiation and cornification of keratinocytes, the primary cell type of the epidermis. In humans, the complex is located on a 1.9 Mbp stretch within chromosome 1q21. The proteins encoded by EDC genes are closely related in terms of function, and evolutionarily they belong to three distinct gene families: the cornified envelope precursor family, the S100 protein family and the S100 fused type protein (SFTP) family.
Chromosome 1 open reading frame 68, or C1orf68, is a human gene which encodes for skin-specific protein 32. C1orf68 gene is expressed in the skin, is a part of the epidermal differentiation complex, and potentially plays a role in epidermal cornification, and epidermal barrier function.