Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent biochemical advances have contributed to clarification of certain skin diseases and metabolic disturbances with predominantly cutaneous symptoms. This is illustrated by the various forms of porphyria. Today we differentiate four hepatic forms: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria and porphyria cutanea tarda, and two erythropoietic forms: congenital erythropoietic porphyria and erythropoietic protoporphyria, all of which are due to an inborn enzymatic deficiency of the heme biosynthesis. From the different forms of ichthyosis, the X-recessive ichthyosis has an underlying enzymatic deficiency of the steroid sulfatase, which seems of significance in the disturbance of keratinization. In epidermolysis bullosa dystrophica type Hallopeau-Siemens an increased collagenase activity was detected. Inhibition of this enzyme by phenytoin results in improvement of the blistering in this genodermatosis. The etiology and pathogenesis of psoriasis are unclear despite extensive efforts. The recently detected deficiency of the arylhydrocarbon-hydroxylase and its inducibility must be confirmed, additionally its significance in the pathogenesis of this disease is yet to be evaluated.
 ...
PMID:[Progress in dermatology: new biochemical aspects]. 629 Mar 59

In a series of transgenic mice, the human tissue collagenase gene was expressed in the suprabasal layer of the skin epidermis. Visually, the mice had dry and scaly skin which upon histological analysis revealed acanthosis, hyperkeratosis, and epidermal hyperplasia. At the ultrastructural level, intercellular granular materials were absent in the transgenic skin epidermis but contact was maintained through the intact desmosomes. Despite a diversity of underlying etiologies, similar morphological hyperproliferative changes in the epidermis are observed in the human skin diseases of lamellar ichthyosis, atopic dermatitis, and psoriasis. Subsequent experiments demonstrate that when the transgenic mouse skin was treated once with an initiator (7,12-dimethyl-benz[a]anthracene) and then twice weekly with a promoter (12-O-tetradecanoylphorbol-13-acetate), there was a marked increase in tumor incidence among transgenic mice compared with that among control littermates. These experiments demonstrate that by overexpressing the highly specific proteolytic enzyme collagenase, a cascade of events leading to profound morphological changes which augment the sensitivity of the skin towards carcinogenesis is initiated in the epidermis.
 ...
PMID:Collagenase expression in transgenic mouse skin causes hyperkeratosis and acanthosis and increases susceptibility to tumorigenesis. 756 25