Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Effects of a natural complex of cytokines secreted by peripheral blood leukocytes on the healing of perforating wounds of the cornea were studied in 28 rabbits (14 animals in control and 14 in experimental groups). The process of healing of similar cut wounds of the cornea during local application of cytostatics was assessed by morphological and morphometric methods on days 1, 3, 7, 14, and 30 after the injury. Two periods, early and late, were distinguished in the morphogenesis of healing of a cut wound of the cornea under the effect of natural cytokines. The cytokines enhanced neutrophil migration to the wound canal in the early period of morphogenesis, this accelerating fibrin resorption, which was followed by filling of the wound canal with keratoblastic proliferate. In the late period of morphogenesis of wound healing (days 14-30) the functional activity of fibroblasts was increased, this being conducive to activation of collagenization of cicatricial tissue and resorption of the cicatrix as a result of a possible increase of collagenase release under the effect of cytokines. The possible mechanism of regulating effect of cytokines on corneal repair is discussed.
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PMID:[Mechanism regulating healing of perforating wounds of the cornea by natural cytokine complex]. 860 30

We have immunopurified and characterized a new glycoprotein of the extracellular matrix, using a monoclonal antibody obtained after immunization with fibril-associated collagens extracted from bovine tendon. In polyacrylamide gels, the protein migrates at about 350 kDa molecular mass. The protein is insensitive to bacterial collagenase, and no disulfide-linked aggregates could be detected; sugars were stained with periodic acid-Schiff's reagent. Amino acid analysis and sequencing of tryptic peptides failed to detect any similarity with known proteins. By rotary shadowing experiments, the protein was observed as flexible, unbranched structures, approximately 150 nm long, with a small globule at one end. Investigation of the tissue distribution of the protein in fetal bovine tissues by immunofluorescence resulted in labeling in extracellular matrices with loosely packed collagen fibrils, such as the peritendineum, embryonic skin and kidney glomeruli; cornea, cartilage matrix and bone were not labeled. Ultrastructural immunolocalization in dermis and in mesangium of glomeruli showed that the protein always occurred in the vicinity of collagen fibrils. In view of its tissue distribution and molecular shape, we postulate that this protein is important in the properties of the extrafibrillar environment. By reference to its shape as observed by rotary shadowing, we propose the name 'flexilin' for this extracellular matrix glycoprotein.
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PMID:Flexilin: a new extracellular matrix glycoprotein localized on collagen fibrils. 878 83

Delayed re-epithelialization of the cornea after injury usually precedes stromal ulceration. Previous findings using a rat thermal injury model suggested that re-epithelialization is impeded by products of resident corneal cells, which destroy adhesive structures at the basement membrane zone. In this study, we provide additional evidence for this concept. Failure to re-epithelialize was found to correlate with an increase in the amounts of gelatinolytic matrix metalloproteinases present in the rat cornea. One of these gelatinases, gelatinase B, is synthesized by the resident corneal cells, and inhibitions of its synthesis correlated with inhibition of basement membrane dissolution. The matrix metalloproteinases collagenase and stromelysin are also synthesized by resident corneal cells in thermally injured corneas of rabbits, but the timing of bulk enzyme synthesis correlated more closely with deposition of repair tissue in the stroma than with failure to re-epithelialize. Nevertheless, in human corneas with repair defects, gelatinase B and collagenase are synthesized by cells in the basal layer of the epithelium directly adjacent to the basement membrane, suggesting that both could participate in dissolution of this structure. Importantly, treatment of thermally injured corneas with a synthetic inhibitor of matrix metalloproteinases significantly improved basement membrane integrity. These data support the concept that over-expression of matrix metalloproteinases by resident corneal cells impedes re-epithelialization after some types of corneal injury.
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PMID:Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury. 886 76

Chemical injuries of the eye may produce extensive damage to the ocular surface epithelium, cornea, and anterior segment, resulting in permanent unilateral or bilateral visual impairment. Pathophysiological events which may influence the final visual prognosis and which are amenable to therapeutic modulation include 1) ocular surface injury, repair, and differentiation, 2) corneal stromal matrix injury, repair and/or ulceration, and 3) corneal and stromal inflammation. Immediately following chemical injury, it is important to estimate and clinically grade the severity of limbal stem cell injury (by assessing the degree of limbal, conjunctival, and scleral ischemia and necrosis) and intraocular penetration of the noxious agent (by assessing clarity of the corneal stroma and anterior segment abnormalities). Immediate therapy is directed toward prompt irrigation and removal of any remaining reservoir of chemical contact with the eye. Initial medical therapy is directed promoting re-epithelialization and transdifferentiation of the ocular surface, augmenting corneal repair by supporting keratocyte collagen production and minimizing ulceration related to collagenase activity, and controlling inflammation. Early surgical therapy if indicated, is directed toward removal of necrotic corneal epithelium and conjunctiva, prompt re-establishment of an adequate limbal vascularity, and re-establishment of limbal stem cell population early in the clinical course, if sufficient evidence exists of complete limbal stem cell loss. Re-establishment of limbal stem cells by limbal autograft or allograft transplantation, or by transfer in conjunction with large diameter penetrating keratoplasty, may facilitate development of an intact, phenotypically correct corneal epithelium. Limbal stem cell transplantation may prevent the development of fibrovascular pannus or sterile corneal corneal ulceration, simplify visual rehabilitation, and improve the visual prognosis. Advances in ocular surface transplantation techniques which allow late attempts at visual rehabilitation of a scarred and vascularized cornea include limbal stem cell transplantation for incomplete transdifferentiation and persistent corneal epithelial dysfunction, and conjunctival and/or mucosal membrane transplantation for ocular surface mechanical dysfunction. Rehabilitation of the ocular surface may be followed, if necessary, by standard penetrating keratoplasty if all aspects of ocular surface rehabilitation are complete, or by large diameter penetrating keratoplasty if successful limbal stem cell transplantation cannot be achieved but other ocular surface rehabilitation is complete.
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PMID:Chemical injuries of the eye: current concepts in pathophysiology and therapy. 910 67

The extracellular matrix (ECM) plays a crucial role in cell adhesion, differentiation and wound-healing. Its stability is tightly controlled by enzymes that regulate the metabolism of its components (e.g collagen, fibronectin, laminin). We have found that in the cornea, a potent lipid inflammatory mediator platelet-activating factor (PAF) activates the expression of two metalloproteinases (MMP-1 and MMP-9) as well as urokinase-plasminogen activator (uPA). uPA is of particular interest because, as a serine protease, it is at the top of the protease cascade. PAF may contribute to the destruction of the ECM and the formation of epithelial defects and corneal ulcers by activating uPA and then proteases. We also investigated how several PAF antagonists with different binding affinities can block the expression of the uPA gene. Our results suggest that PAF antagonists with affinities for intracellular binding sites and/or specific structures derived from triazolobenzodiazepine could be of therapeutic use to limit the breakdown of the ECM and the development of ulcer formation.
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PMID:PAF antagonists as possible inhibitors of corneal epithelial defects and ulceration. 918 44

Collagen IX, a structural component of the extracellular matrix of connective tissues, is synthesized as long and short forms which contain or lack, respectively, a 27 kDa non-collagenous (NC) 4 domain at the N-terminus of the alpha 1(IX) chain of the molecule. The long form occurs in cartilage and developing cornea, but not in vitreous, suggesting a specialized function for the NC4 domain, perhaps by interacting with other macromolecules. To test this hypothesis, embryonic chick cartilage was treated with DTSSP, dissociated with bacterial collagenase, and the NC4-containing DTSSP-cross-linked protein complexes examined and purified. Analysis of cartilage extracts using an anti-NC4 antibody, and of purified NC4-containing complexes, identified a predominant NC4 dimer. A naturally-occurring N-terminal fragment of the alpha 1(IX) chain, whose size is equivalent to the NC4-COL3-NC3 domains of the chain, was identified. Association of collagen IX molecules via NC4 domains and the existence of a cleavage site close to the NC3 domain of the molecule are likely to be of primary importance in the growth and remodeling processes of cartilage, in health and disease.
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PMID:Collagen IX: evidence for a structural association between NC4 domains in cartilage and a novel cleavage site in the alpha 1(IX) chain. 955 Feb 66

We examined the effect of matrix metalloproteinase (MMP) inhibitor (CS-610) on experimental pseudomonal corneal ulceration by clinical and histological evaluation. Intrastromal injection of 3.5 microliters sterile culture broth of P. aeruginosa, IID-1117 (13.5 unit Type I collagenase equivalent proteinase activities), was done to induce corneal ulcers in guinea pigs. The animals were divided into two groups of 23 each. The CS-610 group received topical CS-610 (400 micrograms/ml) treatment at 2-hour intervals and the control group received only the vehicle of CS-610 at the same intervals. In the control group, corneas developed acute corneal damage following corneal ulcerations at 6-12 hours. In the CS-610 group, these corneal lesions were inhibited in most of the eyes (p < 0.01). In the late period, as inflammatory cells migrated into the cornea, some animals of the CS-610 group developed corneal ulcer. The results indicated that CS-610 had a potent inhibitory activity against pseudomonal proteinases in vivo. The results also suggested that the mechanism of the ulceration model involved not only pseudomonal proteinases but also endogenous responses.
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PMID:[Effect of matrix metalloproteinase inhibitor on experimental pseudomonal corneal ulceration]. 985 15

Healing of corneal wounds is a complex process involving epithelial, keratocyte, and endothelial interactions that are affected by their associations with wound bed matrix and by cytokine availability and activation. The spectrum of possible cellular-matrix-growth factor interactions is indeed great and growing. Several of the significant contributions made during the past year include development of an organotypic organ culture model of the cornea that allows in vitro assembly of the epithelial extracellular matrix-anchoring complex, demonstration of epithelial synthesis of Bowman's layer collagens, demonstration of transforming growth factor-beta 2's inhibition of stromal cell collagenase synthesis, and demonstration of the paracrine pathway of keratinocyte growth factor action in the cornea.
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PMID:Extracellular matrix and growth factors in corneal wound healing. 1015 Aug 80

The thinning of the cornea that occurs in keratoconus has been well described; however, the mechanism of tissue degradation remains unknown. Elevated proteinase activity is one possibility and approximately 20 publications over the last 20 years have addressed this hypothesis. Early studies reported increased collagenase and gelatinase activities in the medium of keratoconus corneal cultures. After the characterization of the matrix metalloproteinase (MMP) enzymes, studies focused on the expression of specific MMPs, in particular the gelatinases, MMP-2 and MMP-9. Matrix metalloproteinase-2 was found to be the major MMP of the cornea and was constitutively produced in normal tissue, whereas MMP-9 expression was induced by various stimuli, including phorbol esters and even tissue culturing. These studies suggested that there were no differences in the amounts or states of activation of MMP between normal and keratoconus corneas, although the amounts of some proteinase inhibitors, including tissue inhibitors of metalloproteinases, alpha-1-proteinase inhibitor and alpha-2-macroglobulin, were decreased in keratoconus. Most recently, the lysosomal proteinases, cathepsin B and cathepsin G were reported to be elevated in keratoconus corneas, and it is possible that it was cathepsin activity, not MMP activity, that was measured in some early studies. Nevertheless, there are now about 20 human MMPs identified and it is possible that some of these, other than the well known collagenase (MMP-1) and gelatinases (MMP-2 and MMP-9), could be implicated in the pathology of keratoconus. Studies have begun to address more recently described MMPs and it has been reported that the membrane-bound MT1-MMP (MMP-14), which activates latent MMP-2, was found to have increased expression in keratoconus corneas, whereas the stromelysins, MMP-3 and MMP-10, were not.
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PMID:Is the corneal degradation in keratoconus caused by matrix-metalloproteinases? 1177

Degradation of basement membrane by metalloproteinases (MMP) is a critical step in tumor angiogenesis. To evaluate in vitro angiogenesis, several models have been employed, including bovine cornea, fenestrated rat brain, Matrigel, and others. These models did not provide quantitative analysis of capillary formation. The current study aimed for a novel approach to in vitro assay of angiogenesis with a "wet scanning electron microscope (SEM)" to investigate suppression of tumor angiogenesis by the MMP inhibitor, SI-27. The effects of noncytotoxic concentrations of SI-27 (1-100 microM) were determined on nonmitogenic vascular endothelial growth factor (VEGF) (10 ng/ml)-mediated cell motility and in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). Activities of MMP and tissue inhibitor of metalloproteinase (TIMP) were determined by enzyme-linked immunosorbent assay (ELISA). Subsequently, the inhibitory effect of SI-27 was examined on in vitro angiogenesis stimulated by supernatants of human glioma cell lines (U87MG, U251MG, or U373MG). In vitro angiogenesis was quantitatively analyzed with a variable-pressure SEM. Cell motility and in vitro angiogenesis by HUVECs were significantly increased by VEGF along with elevated MMP-1 and -2 activity, whereas SI-27 significantly suppressed VEGF-mediated in vitro angiogenesis and inactivated both MMP-1 and MMP-2, but not inhibited cell motility. The angiogenesis promoted by glioma supernatants showed a significant reduction in the presence of SI-27. SI-27, a novel MMP inhibitor, inhibited tumor angiogenesis in vitro. It can be anticipated to prevent tumor growth through its angiosuppressive effect. Quantitative analysis with a variable-pressure SEM is a novel approach to in vitro angiogenesis assay.
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PMID:Novel approach to analysis of in vitro tumor angiogenesis with a variable-pressure scanning electron microscope: suppression by matrix metalloproteinase inhibitor SI-27. 1190 79


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