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

Recently we reported that a kind of serine protease, SH protease, and collagenase might be involved in blister formation and, furthermore, that the cooperative action of these three proteases was essential for blister formation in recessive dystrophic epidermolysis bullosa. In this study we examined the inhibitory effect of clinically usable serine protease inhibitors for blister formation in organ culture and in clinical trials of recessive dystrophic epidermolysis bullosa patients. Camostat mesylate, a synthetic serine protease inhibitor that is available for the treatment of chronic pancreatitis, demonstrated a striking effect of inhibiting blistering in organ culture of normal human skin with recessive dystrophic epidermolysis bullosa blister fluids. Subsequently we administered camostat mesylate by topical application to four patients with recessive dystrophic epidermolysis bullosa to assess its ability to reduce blistering. Therapeutic response was favorable; a significant effect in decreasing the number of blisters was observed in three of four patients. These findings actually supported the hypothesis that a kind of serine protease had a close relationship with blistering in recessive dystrophic epidermolysis bullosa and that therapy with a clinically usable protease inhibitor was useful for the treatment of this disease.
J Am Acad Dermatol 1988 Jun
PMID:Protease inhibitor therapy for recessive dystrophic epidermolysis bullosa. In vitro effect and clinical trial with camostat mesylate. 338 39

In order to separate the changes of actinic damage from those of simple aging, we studied the elastic fibers in low and high sun-exposed skins of normal subjects at different ages. Low sun-exposed skin shows chronologic aging lesions only. These begin at age 30 with a disappearance of oxytalan fibers and with some abnormalities in the reticular and deep dermis; at age 40, aging changes are established: no oxytalan fibers, marked abnormalities, and lysis of elaunic and elastic fibers. In high sun-exposed skin, age-related lesions also occur but are associated with more or less precocious elastotic degeneration in reticular and deep dermis. Both types of aging fibers are revealed by the antielastin antibody HB 8, disappear with elastase, but resist collagenase. Actinic elastosis clearly originates from elastin. The two types of change differ in electron microscopic appearance: with spontaneous aging, elastic fibers are disintegrated (loose and porous fibers); in actinic damage, elastotic fibers are thicker and have accentuated microfibril dense masses. The age-associated lesions could be due to the activity of protease of fibroblastic origin whereas the elastotic degeneration is probably due to the actinic stimulation of fibroblasts.
Int J Dermatol 1988 Jun
PMID:The elastic tissue of the skin. A comparison of spontaneous and actinic (solar) aging. 339 28

The epidermolysis bullosa acquisita antigen is a major constituent of the basement membrane zone beneath stratified squamous epithelium. The antigen which is recognized in extracts of skin basement membrane by Western blot analysis with polyclonal or monoclonal antiepidermolysis bullosa acquisita antigen antibodies as 2 chains (a major chain of 290,000 and a minor chain of 145,000) has a native molecular weight over 800,000. Both epidermolysis bullosa acquisita antigen chains contain carbohydrate and the 290K chain is sensitive to collagenase.
J Invest Dermatol 1986 Jun
PMID:Epidermolysis bullosa acquisita antigen, a new major component of cutaneous basement membrane, is a glycoprotein with collagenous domains. 351 86

Reduction of a commercially available, pepsin-solubilized, bovine dermal collagen (Vitrogen 100) with sodium [3H]borohydride provided radiolabeled collagen preparations with specific activities ranging from 7.1-12.0 muCi/mg collagen. These specific activities were 2-3 times greater than those obtained by reduction of intact rat tail tendon collagen under similar conditions. The alpha, beta, and higher aggregate components of type I collagen were radiolabeled as well as the alpha component of a small amount of type III collagen present in the samples. Fractionation of cyanogen bromide peptides showed that alpha 1(I)CB7, alpha 1(I)CB8, and alpha 2(I)CB3,5 were the predominant peptides labeled by this procedure. Amino acid analysis indicated that the majority of the radioactivity was in reducible cross-links, precursors of these cross-links, and in hexosyllysine residues. Reconstitution experiments comparing this radiolabeled collagen with nonlabeled collagen showed them to be indistinguishable. Bacterial collagenase digestion of this reconstituted fibrillar collagen in both a lightly cross-linked (glutaraldehyde 0.0075%) and noncross-linked form provided evidence that digestion of labeled and nonlabeled collagens proceeded at similar rates. Thus, labeling did not change the properties of the collagen. Cross-linking made the preparation refractory to proteolytic degradation. Injection of fibrillar collagen preparations, spiked with radiolabeled collagen, into the guinea pig dermis followed by quantitation of the amount of radioactivity recovered from implant sites as a function of time, indicated that the lightly cross-linked samples also were more resistant to degradation in vivo than the noncross-linked preparation. The half-life of noncross-linked collagen was about 4 days while that of the cross-linked collagen was about 25 days. These degradation rates were much faster than observed for similar, nonlabeled samples injected into the dermis of humans, presumably due to a higher metabolic activity in the guinea pig dermis.
J Invest Dermatol 1986 Jun
PMID:Preparation of [3H]collagen for studies of the biologic fate of xenogenic collagen implants in vivo. 371 80

Ten patients with necrobiosis lipoidica lesions were studied. Five patients had diabetes mellitus. The age of the patients varied from 15 to 73 years and the duration of the skin lesions was from 2 to 20 years. Histologically, the lesions were characterized by degeneration of collagen and elastin. In some lesions elastin fibers could be seen in areas devoid of normal-looking collagen. Electron microscopy revealed loss of cross-striation of collagen fibrils and a marked variation in the diameter of individual collagen fibrils. The concentration of collagen, measured by assay of hydroxy-proline, a collagen-specific amino acid, was markedly decreased in the lesional skin, but the ratio of type I/III collagen was unchanged in the affected skin. Fibroblasts established from affected skin synthesized less collagen than cells derived from healthy-looking skin. The decreased collagen synthesis was due to a decreased amount of messenger RNA for type I procollagen, measured by hybridization with a specific human cDNA clone. The production of collagenase by these fibroblasts was not increased. Our results thus indicate that in necrobiosis lipoidica lesions, collagen fibrils are defective and the amount of collagen is reduced, probably due to decreased synthesis of collagen by affected fibroblasts.
J Invest Dermatol 1987 Feb
PMID:Necrobiosis lipoidica: ultrastructural and biochemical demonstration of a collagen defect. 380 59

The specific factors which induce blister formation in recessive dystrophic epidermolysis bullosa (RDEB) and epidermolysis bullosa simplex (EBS) were studied by culturing normal human skin with blister fluid from patients with RDEB and EBS. When skin from a healthy person was cultured with RDEB blister fluid, it developed a clean subepidermal blister with histology similar to that of a RDEB blister. The specific factor(s) which induced this subepidermal blister was inactivated by heat (60 degrees C, 30 min), trypsin digestion and by treating with EDTA, EGTA, alpha 2-macroglobulin, soybean trypsin inhibitor (SBTI) or N-ethylmaleimide (NEM), but was not affected by dialysis. These findings suggest that the active factor(s) in the blister fluid from patients with RDEB might include collagenase, neutral thiol protease and trypsin-like protease. By contrast, when normal skin was cultured with EBS blister fluid, this produced a clean intra-epidermal blister with histology similar to that of an EBS blister. The specific factor(s) inducing the intra-epidermal blister was inactivated by heat (60 degrees C, 30 min), trypsin digestion and by treating with NEM, but was not affected by dialysis, divalent cation chelators (EGTA, EDTA), alpha 2-macroglobulin, SBTI and pepstatin. These results suggest that the active factor(s) inducing the intra-epidermal blister in EBS might be a neutral SH-protease.
Br J Dermatol 1985 May
PMID:Proteases are responsible for blister formation in recessive dystrophic epidermolysis bullosa and epidermolysis bullosa simplex. 389 Sep 16

The effects of two different polymeric wound dressings and a new collagen matrix (CM) implant on the healing and scarring of full-thickness excision wounds were studied in swine. The synthetic polymers comprised an occlusive O2-impermeable hydrocolloid dressing (HCD) and an occlusive O2-permeable polyurethane film (PUF). The CM implant consisted of an acellular collagen sponge fabricated from purified bovine tendon type I collagen. Wounds were evaluated for granulation tissue--production capacity by measuring 14C proline incorporation into collagenase-sensitive protein. Epidermal resurfacing and wound contraction were measured by computerized morphometric image analysis of wounds made on a tattooed grid. In comparison with air-exposed wounds, the relative collagen synthetic capacity was greater in the granulation tissue of wounds treated with HCD, PUF, or CM with occlusion. Both HCD and PUF accelerated by 40% the epidermal resurfacing over the granulating wound bed. Wound contraction was significantly reduced by CM but was not altered by the occlusive dressings.
J Am Acad Dermatol 1985 Feb
PMID:Dermal wound repair: role of collagen matrix implants and synthetic polymer dressings. 397 42

Recent observations have suggested that retinoids might affect the metabolism of the extracellular matrix of connective tissues. In this study, we examined the effects of tretinoin (all-trans-retinoic acid) and isotretinoin (13-cis-retinoic acid) on the production of procollagen in keloid fibroblast cultures that were characterized by enhanced procollagen synthesis in vitro. The activities of three enzymes relevant to connective tissue metabolism, prolyl hydroxylase, collagenase, and an elastaselike neutral protease were also determined. The results demonstrated that collagen production was markedly reduced in cultures treated with either one of the retinoids. The activity of prolyl hydroxylase, a key enzyme in the intracellular biosynthesis of collagen, was not affected, while the production of collagenase was markedly reduced by the retinoids. In contrast, the activity of an elastaselike neutral protease in the cell culture medium was markedly enhanced by both retinoids. The results, therefore, indicate a differential modulation of connective tissue metabolism by retinoids in keloid cell cultures.
Arch Dermatol 1985 May
PMID:Retinoid modulation of connective tissue metabolism in keloid fibroblast cultures. 399 9

Two siblings with junctional epidermolysis bullosa are described: both survived beyond parturition. They were treated with the usual therapeutic doses of phenytoin, dapsone, prednisolone, and zinc supplements without effect. Investigation of the skin of one of the patients showed that his fibroblasts, collagen synthesis and collagenase levels were normal. In view of the normality of the collagenase levels, it is probably not surprising that phenytoin was ineffective. Electron microscopy demonstrated junctional cleavage without pathology in the dermis itself: abnormal hemidesmosomes were seen as described previously, though it is suggested that this is not the primary abnormality which results in the disease process.
Br J Dermatol 1984 Nov
PMID:Junctional epidermolysis bullosa in two siblings: clinical observations, collagen studies and electron microscopy. 609 44

Mouse monoclonal antibodies to various human epidermal and basement membrane components were formed by immunizing Balb/c mice with ME-180, a line of human cervical carcinoma cells. The spleen cells from hyperimmunized mice were fused with a nonsecreting mouse myeloma cell line using polyethylene glycol. The resulting hybrids were selected by growth in media containing 20% fetal calf serum, hypoxanthine, thymidine, and methotrexate in RPMI-1640 in 24-well Linbro plates. Wells producing antibodies of interest were grown and eventually cloned over an HGPRT- rat fibroblast feeder layer. These cultures were expanded and recloned. Two cloned antibodies of interest are DUX 5.2 and DUX 1.1.3. DUX 5.2 is the mouse IgG1 subclass and reacts with the membranes of ME-180 cells and the human skin epidermal basement membrane zone as shown by direct immunofluorescent microscopy. Ultrastructural localization using electron microscopic immunoperoxidase techniques showed localization of the DUX 5.2 antigen to be beneath the lamina densa; the reaction product may include the anchoring fibrils. Although DUX 5.2 reacts with the normal human basement membrane zone and the basement membrane zone in several diseases, there is no reactivity in the normal, never-blistered skin of patients with dystrophic epidermolysis bullosa (DEB). This suggests that the increased collagenase in the disease may be destroying antigenicity of the antigen recognized by DUX 5.2 or that the antigen may not be present in DEB. This antibody will thus allow early neonatal and prenatal diagnosis in DEB and allow isolation of the structural moiety which is deficient in DEB. DUX 1.1 is an IgM mouse immunoglobulin specific for the cytoplasm of human basal cells. Its reactivity with upper epidermis is significantly less than that seen in the basal layer. All cells of the basal layer stain uniformly. The slight amount of staining in upper cells probably represents dilution of antigen which is not synthesized beyond the basal layer. Basal cells of hair follicles and sweat glands are stained to some degree.
Curr Probl Dermatol 1983
PMID:Monoclonal antibodies to normal and abnormal epithelial antigens. 619 49


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