Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to identify structures in human skin that bind collagenase, sections from frozen or paraffin-embedded skin were incubated with either procollagenase or activated collagenase. After washing, bound procollagenase or collagenase was detected by immunofluorescence microscopy. In normal skin, procollagenase bound only to isolated granular dermal cells that were identified as mast cells on the basis of staining with fluoresceinated avidin and pinacyanol erythrosinate. When mast cells were degranulated by exposure to the ionophore A23187, extracellular granules bound procollagenase. Of various pathologic conditions examined, the highest binding of procollagenase occurred in specimens of urticaria pigmentosa. Procollagenase bound to granular cells and to abundant granules scattered throughout the dermis. Binding could be abolished by pre-treatment of tissue sections with heparinase or by pre-incubation of procollagenase with soluble heparin, suggesting that heparin is the binding agent in the granules. Activated collagenase also bound to dermal mast cells but in addition bound strongly to the dermal collagen. Enzymatic activity of activated collagenase was not inhibited by heparin in concentrations up to 10 mg/ml. There is evidence that mast cell tryptase can contribute to procollagenase activation. This study further supports a role for mast cells in collagenolysis by demonstrating that heparin from mast cells binds procollagenase and possibly serves as a reservoir for procollagenase, which may then subsequently be activated.
J Invest Dermatol 1992 May
PMID:Dermal mast cell granules bind interstitial procollagenase and collagenase. 137 47

To clarify the relationship of the 290 and 145 kDa chains of the epidermolysis bullosa acquisita (EBA) antigen, we subjected urea extracts of skin basement membrane zone (BMZ) proteins and isolated 290 and 145 kDa chains of the EBA antigen cut out of sodium dodecyl sulfate polyacrylamide gels to treatment with clostridial collagenase. When the reaction products were electrophoresed, transblotted, and reacted with EBA patient sera or two monoclonal antibodies to the EBA antigen, the 290 kDa chain was degraded into the 145 kDa band that was resistant to cleavage with collagenase. The 145 kDa domain, isolated after collagenase treatment of the whole BMZ extract, was resistant to degradation by hyaluronidase, chondroitinase ABC, heparinase, and heparitinase but was readily degraded by V-8 protease. These data suggest that the EBA antigen consists of collagen and noncollagen domains of identical size (Mr 145,000), and that the 145 kDa noncollagen domain is generated via degradation of the native 290 kDa species by collagenase.
J Invest Dermatol 1988 Feb
PMID:Epidermolysis bullosa acquisita antigen: relationship between the collagenase-sensitive and -insensitive domains. 282 79

Comparison of the [35S]mucopolysaccharides extracted after in vitro incubation of skin biopsy specimens from nonlesional and lesional sites of a patient with mastocytosis showed that lesional sites incorporated sulfate into heparin. After in vitro incorporation of the [35S]sulfate, the tissues were extracted sequentially by a 3-step procedure which utilized high salt concentrations, enzymatic digestion and base hydrolysis to liberate essentially all the counts. The extracted [35S]mucopolysaccharides were separated from free [35S]sulfate, histamine, protein, and hyaluronic acid by ion-exchange chromatography utilizing Dowex 1. The [35S]mucopolysaccharide extracts of the nonlesional skin were completely degraded by treatment with chondroitinase ABC, as they age predominantly dermatan sulfate with small amounts of chondroitin sulfates. The absolute quantity of sulfated mucopolysaccharides after Dowex 1 chromatography in micrograms of uronic acid per mg wet weight of starting tissue was higher in the lesional than the nonlesional specimen, while the specific incorporation of [35S]sulfate per microgram of uronic acid was the same. Approximately one-half of the [35S]mucopolysaccharides obtained in the 3 sequential extracts of lesional tissue was resistant to degradation by chondroitinase ABC as determined by gel filtration before and after enzyme treatment, indicating the presence of sulfated mucopolysaccharides in addition to chondroitin and dermatan sulfates. Heparinase treatment of the chondroitinase ABC-resistant [35S]mucopolysaccharides followed by gel filtration revealed an equal distribution of label between heparin and heparinase-resistant material presumed to be heparan sulfate. Heparin was also directly demonstrated in extracts of lesional mastocytosis skin by chemical and functional criteria.
J Invest Dermatol 1980 Apr
PMID:Identification of sulfated mucopolysaccharides including heparin in the lesional skin of a patient with mastocytosis. 644 88

Fibroblast migration from the peri-wound collagenous stroma into the fibrin-laden wound is critical for granulation tissue formation and subsequent healing. Previously we found that fibroblast transmigration from a collagen matrix into a fibrin matrix required fibronectin (FN). Integrins alpha4beta1, alpha5beta1, and alphavbeta3 and dermatan sulfate CD44 were required for this invasive migration. Here we demonstrated that syndecan-4, a transmembrane heparan sulfate (HS) proteoglycan, known to bind FN, is also required for fibroblast invasive migration of a fibrin/FN gel. This conclusion was based on fibroblast migration using two independent means of disrupting syndecan-4: heparinase degradation of HS glycosaminoglycans or suppression of syndecan-4 core protein with antisense oligodeoxynucleotides. Isolated syndecan-4 from these fibroblasts bound Hep II recombinant constructs FN III12-V15>FN III12-15>FN III12-14 but did not bind the IIICS (V) domain. Furthermore, platelet-derived growth factor (PDGF), which is required to stimulate fibroblast migration, markedly increased cell levels of syndecan-4 core protein in a time and concentration-dependent fashion. PDGF also induced upregulation of syndecan-4 at transcriptional level as determined by RT-PCR. These results demonstrate that syndecan-4 is essential for fibroblast invasive migration into fibrin clot and that PDGF, the stimulus for migration, induces increased syndecan-4 core protein expression.
J Invest Dermatol 2005 May
PMID:Three-dimensional migration of human adult dermal fibroblasts from collagen lattices into fibrin/fibronectin gels requires syndecan-4 proteoglycan. 1585 29