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LEKTI-2
Lympho-epithelial Kazal-type related inhibitor 2 (LEKTI-2) is a protein encoded by the ''SPINK9'' gene in humans. ''SPINK9'' is a member of a gene family cluster located on chromosome 5q33.1, which includes ''SPINK5'' and ''SPINK6''. LEKTI-2 is an inhibitor of KLK5. Desquamation The outer layer of the epidermis is called the stratum corneum. In the stratum corneum terminally differentiated corneocytes are held together by corneodesmosomes. In order for desquamation to occur, corneodesmosomes need to be fully degraded. KLK5 and KLK7 are two serine proteases that degrade corneodesmosomes. LEKTI-2 regulates corneodesmosome degradation by inhibiting KLK5. In acral (palm and sole) skin, where desquamation needs to be delayed, ''SPINK9'' expression is strongly upregulated. The resulting high level of LEKTI-2 delays corneodesmosome degradation, thereby allowing the epidermis to form a thick protective stratum corneum layer. Clinical Significance SPINK9 is overexpressed in lichen simplex ...
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Chromosome 5
Chromosome 5 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 5 spans about 181 million base pairs (the building blocks of DNA) and represents almost 6% of the total DNA in cells. Chromosome 5 is the 5th largest human chromosome, yet has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of non-coding and syntenic conservation with non-mammalian vertebrates, suggesting they are functionally constrained. Because chromosome 5 is responsible for many forms of growth and development (cell divisions) changes may cause cancers. One example would be acute myeloid leukemia (AML). Genes Number of genes The following are some of the gene count estimates of human chromosome 5. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies (for technical details, see gene prediction ...
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SPINK5
Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known as serine protease inhibitor Kazal-type 5 (SPINK5) is a protein that in humans is encoded by the ''SPINK5'' gene. Structure and function LEKTI is a large multidomain serine protease inhibitor expressed in stratified epithelial tissue. It consists of 15 domains that are cleaved into smaller, functional fragments by the protease furin. Only two of these domains (2 and 15) contain 6 evenly spaced cysteines responsible for 3 intramolecular disulfide bonds characteristic of Kazal-type related inhibitors. The remaining domains contain 4 cysteines. These disulfide bonds force the molecule into a rigid conformation that enables the protein to interact with a target protease via an extended beta-sheet. All domains (excepting 1, 2 and 15) contain an arginine at P1, indicating trypsin-like proteases are the likely targets. In the epidermis, LEKTI is implicated in the regulation of desquamation via its ability to selective ...
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SPINK6
Serine protease inhibitor Kazal-type 6 (SPINK6) is a protein encoded by the ''SPINK6'' gene in humans. It is a potent inhibitor of epidermal proteases involved in maintaining skin homeostasis, including KLK5, KLK7 and KLK14. ''SPINK6'' is a member of a gene family cluster located on chromosome 5q33.1, which includes ''SPINK5'' and ''SPINK9 Lympho-epithelial Kazal-type related inhibitor 2 (LEKTI-2) is a protein encoded by the ''SPINK9'' gene in humans. ''SPINK9'' is a member of a gene family cluster located on chromosome 5q33.1, which includes '' SPINK5'' and '' SPINK6''. LEKTI-2 is ...''. See also * Kazal-type serine protease inhibitor domain References Proteins {{gene-5-stub ...
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KLK5
Kallikrein-5, formerly known as stratum corneum tryptic enzyme (SCTE), is a serine protease expressed in the epidermis. In humans it is encoded by the ''KLK5'' gene. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its expression is up-regulated by estrogens and progestins. Alternative splicing results in multiple transcript variants encoding the same protein. KLK5 has been suggested to regulate cell shedding (desquamation) in conjunction with KLK7 and KLK14, given its ability to degrade proteins which form the extracellular component of cell junctions in the stratum corneum. It is proposed that KLK5 regulates this process since it is able to self-activate in addition to activating KLK7 and KLK14. References Further reading * * * * * * * * * * * * * * * * * External links * The MEROPS MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The c ...
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Epidermis
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 epidermis is composed of multiple layers of flattened cells that overlie a base layer (stratum basale) composed of columnar cells arranged perpendicularly. The layers of cells develop from stem cells in the basal layer. The human epidermis is a familiar example of epithelium, particularly a stratified squamous epithelium. The word epidermis is derived through Latin , itself and . Something related to or part of the epidermis is termed epidermal. Structure Cellular components The epidermis primarily consists of keratinocytes ( proliferating basal and differentiated suprabasal), which comprise 90% of its cells, but also contains melanocytes, Langerhans ...
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Stratum Corneum
The stratum corneum (Latin for 'horny layer') is the outermost layer of the epidermis. The human stratum corneum comprises several levels of flattened corneocytes that are divided into two layers: the ''stratum disjunctum'' and ''stratum compactum''. The skin's protective acid mantle and lipid barrier sit on top of the stratum disjunctum. The stratum disjunctum is the uppermost and loosest layer of skin. The stratum compactum is the comparatively deeper, more compacted and more cohesive part of the stratum corneum. The corneocytes of the stratum disjunctum are larger, more rigid and more hydrophobic than that of the stratum compactum. The stratum corneum is the dead tissue that performs protective and adaptive physiological functions including mechanical shear, impact resistance, water flux and hydration regulation, microbial proliferation and invasion regulation, initiation of inflammation through cytokine activation and dendritic cell activity, and selective permeability to exc ...
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Desquamation
Desquamation occurs when the outermost layer of a tissue, such as the skin, is shed. The term is . Physiologic desquamation Keratinocytes are the predominant cells of the epidermis, the outermost layer of the skin. Living keratinocytes reside in the basal, spinous, or granular layers of the epidermis. The outermost layer of the epidermis is called the Stratum corneum and it is composed of terminally differentiated keratinocytes, the Corneocytes. In the absence of disease, desquamation occurs when corneocytes are individually shed unnoticeably from the surface of the skin. Typically the time it takes for a corneocyte to be formed and then shed is about 14 weeks but this time can vary depending on the anatomical location that the skin is covering. For example, desquamation occurs more slowly at acral (palm and sole) surfaces and more rapidly where the skin is thin, such as the eyelids. Normal desquamation can be visualized by immersing skin in warm or hot water. This induces the out ...
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KLK7
Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the ''KLK7'' gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19 (19q13). Gene Alternative splicing of the ''KLK7'' gene results in two transcript variants encoding the same protein. Function KLK7 is secreted as an inactive zymogen in the stratum granulosum layer of the epidermis, requiring proteolytic cleavage of the short N-terminal pro-region to liberate activated enzyme. This may be performed by KLK5 or matriptase, which are ''in vitro'' activators of KLK7. Once active, KLK7 is able to cleave desmocollin and corneodesmosin. These proteins constitute the extracellular component of corneodesmosomes, intercellular cohesive structures which link the intermediate filaments ...
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Lichen Simplex Chronicus
Lichen simplex chronicus (LSC) is thick leathery skin with exaggerated skin markings caused by sudden itching and excessive rubbing and scratching. It generally results in small bumps, patches, scratch marks and scale. It typically affects the neck, scalp, upper eyelids, ears, palms, soles, ankles, wrists, genital areas and bottom. It often develops gradually and the scratching becomes a habit. Signs and symptoms People burdened with LSC report pruritus, followed by uncontrollable scratching of the same body region, excessively. Most common sites of LSC are the sides of the neck, the scalp, ankles, vulva, pubis, scrotum, and extensor sides of the forearms. However, due to the stigma associated with chronic scratching, some patients will not admit to chronic rubbing or abrasion. The skin may become thickened and hyperpigmented (lichenified) as a direct result of chronic excoriation. Typically this period of increased scratching is associated with stressors. Causes This is a ...
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Actinic Keratosis
Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . Actinic keratosis is a disorder (''-osis'') of epidermal keratinocytes that is induced by ultraviolet (UV) light exposure ('' actin-''). These growths are more common in fair-skinned people and those who are frequently in the sun. They are believed to form when skin gets damaged by UV radiation from the sun or indoor tanning beds, usually over the course of decades. Given their pre-cancerous nature, if left untreated, they may turn into a type of skin cancer called squamous cell carcinoma. Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma, so treatment by a dermatologist is recommended. Actinic keratoses characteristically appear as thick, scaly, or crusty areas that often feel dry or rough. Size commonly ranges be ...
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Squamous Cell Carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the lining of the respiratory and digestive tracts. Common types include: * Squamous-cell skin cancer: A type of skin cancer * Squamous-cell carcinoma of the lung: A type of lung cancer * Squamous-cell thyroid carcinoma: A type of thyroid cancer * Esophageal squamous-cell carcinoma: A type of esophageal cancer * Squamous-cell carcinoma of the vagina: A type of vaginal cancer Despite sharing the name "squamous-cell carcinoma", the SCCs of different body sites can show differences in their presented symptoms, natural history, prognosis, and response to treatment. By body location Human papillomavirus infection has been associated with SCCs of the oropharynx, lung, fingers, and anogenital region. Head and neck cancer About 90% of cases ...
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