Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Identification of tissue-specific mechanisms involved in the pathophysiology of inflammatory skin diseases could offer new possibilities to develop effective therapies with fewer systemic effects. The serine protease stratum corneum chymotryptic enzyme is preferentially expressed in cornifying epithelia. We have previously reported on increased expression of the stratum corneum chymotryptic enzyme in psoriasis. Here is reported an increased epidermal expression of stratum corneum chymotryptic enzyme also found in chronic lesions of atopic dermatitis. Transgenic mice expressing human stratum corneum chymotryptic enzyme in suprabasal epidermal keratinocytes were found to develop pathologic skin changes with increased epidermal thickness, hyperkeratosis, dermal inflammation, and severe pruritus. The results suggest that stratum corneum chymotryptic enzyme may be involved in the pathogenesis of inflammatory skin diseases, and that stratum corneum chymotryptic enzyme and related enzymes should be evaluated as potential targets for new therapies.
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PMID:Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis. 1187 83

Stratum corneum chymotryptic enzyme (SCCE; also known as kallikrein 7) is a serine protease that is preferentially expressed in cornifying epithelia and possibly involved in the desquamation process. We have recently described transgenic mice over-expressing human SCCE in the epidermis showing increased epidermal thickness, hyperkeratosis, and an apparent dermal inflammation with pruritus. This suggests that SCCE may be involved in the pathophysiology of inflammatory skin diseases. We therefore carried out a further characterization of the skin changes observed in scce-transgenic mice. An increase in number of dermal cells was verified by stereological measurements showing a more than twofold increase of the volume fraction of dermis occupied by cell nuclei. In some, but not all, animals the number of dermal mast cells was increased. The dermal cell infiltrate was shown to consist mainly of macrophages and granulocytes. The number of epidermal and dermal T-lymphocytes was not increased. Dermal changes were found in transgenic animals before the age they became pruritic. No increase in interferon-gamma expression could be detected in the skin of transgenic animals. In spite of this, keratinocytes of adult transgenic mice were found to express MHC II antigen. We suggest that increased expression and/or activity of epidermal SCCE may lead to skin changes that contribute to development and maintenance of inflammatory skin diseases.
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PMID:Transgenic mice over-expressing a serine protease in the skin: evidence of interferon gamma-independent MHC II expression by epidermal keratinocytes. 1460 96

Stratum corneum chymotryptic enzyme (SCCE; also known as kallikrein 7) is a serine protease that may have an important role in the skin desquamation process. We have recently described transgenic mice overexpressing human SCCE in suprabasal epidermal keratinocytes, leading to increased epidermal thickness, hyperkeratosis, dermal inflammation and signs of severe pruritus in older animals. In order to further evaluate the scce-transgenic mice as a potential disease model, we compared transgenic animals and wild-type littermates for patterns of epidermal keratin expression, in situ hybridization of scce-mRNA, scratching behaviour and measurements of transepidermal water loss (TEWL). In 3-day-old mice, despite readily detectable amounts of human scce-mRNA in the epidermis of transgenic animals, there were no histological differences in skin appearance, and no differences could be found in epidermal expression of the keratins 5, 6 and 10. In mice 7-8 weeks of age and older, there was strong suprabasal expression of keratins 5 and 6 in the epidermis of transgenic animals, suggesting that the thickened epidermis in these animals is the result of keratinocyte hyperproliferation. In transgenic animals 11 weeks of age and older there was an increased frequency of scratching, suggestive of pruritus, and also signs of a deteriorating skin barrier function, as reflected by an increased TEWL. There was no correlation between increased TEWL and increased frequency of scratching in individual animals, suggesting that the defect barrier function was not an effect of skin damage caused by scratching.
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PMID:Epidermal hyperproliferation and decreased skin barrier function in mice overexpressing stratum corneum chymotryptic enzyme. 1504 Apr 72

Itch is a common symptom in dry skin related to inflammatory skin diseases, normal aging, and systemic diseases such as chronic renal failure, and HIV. However, correlations between itch and objective measures of barrier function and skin dryness such as skin hydration and transepidermal water loss have been rarely found. Recent experimental evidence indicates that damage to the stratum corneum with acetone/ether and water elicits a scratching response in mice and rats. These responses correlate to the number of PGP 9.5 immunoreactive fibers in the epidermis and to FOS-like immunoreactivity in the spinal cord. Other neuromediators involved in the pathogenesis of itch in dry skin are nerve growth factor (NGF), muscarinic acetylcholine receptors, and opiates. Serine proteases such as tryptase and their respective proteinase-activating receptor 2 (PAR2), recently found in both skin and nerves of patients with atopic eczema, suggest that these molecules may have a role in itch in dry skin. This has also been exemplified in the itchy and hyperkeratotic phenotype of the stratum corneum chymotryptic enzyme (SCCE) transgenic mouse model, which is over-expressing a serine protease. Developing inhibitors to these neuropeptides and mediators may be an attractive strategy for anti-itch treatment. The significant progress made in development of moisturizers may have an additional benefit in reducing the itch associated with dry skin. Formulating topical combination therapies containing moisturizers and anti-pruritics can significantly reduce the itch associated with dry skin. This paper will review the current clinical knowledge on the association between dry skin and itch and the recent advances in understanding the pathophysiology of this problem.
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PMID:Dry skin and impairment of barrier function associated with itch - new insights. 1849 19