Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:031673 (collagen)
 124,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secretion of glomerular cell-derived matrix metalloproteinases (MMPs) and their specific inhibitors, TIMP-1,2, may play an important role in the turnover of the glomerular extracellular matrix under basal and pathologic conditions. A 66-68 kd MMP secreted by cultured mesangial cells (MC) with activity against Type IV collagen and gelatin was purified and shown by amino-acid sequence analysis to be identical with a Type IV collagenase/gelatinase secreted by certain transformed tumor cell lines. The expression of the mesangial MMP in vivo was limited within the kidney to a small subset of the intrinsic glomerular mesangial cell population. After induction of acute anti-Thy 1.1 glomerulonephritis, there was a large increment in the number of Type IV collagenase-secreting MC, temporally coincident with the development of mesangial hypercellularity. The expression of the MMP inhibitor protein, TIMP-1, was not changed over this period. Ultrastructural studies localized the mesangial MMP to areas of evolving mesangiolysis and at sites of glomerular basement membrane disruption. Enhanced expression of the mesangial cell-derived Type IV collagenase may contribute to the evolution of glomerular injury in this model of immune complex-mediated glomerulonephritis or may be involved in the extensive matrix remodeling process that accompanies this form of glomerular injury.
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PMID:Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex-mediated glomerulonephritis. 132 65

We have documented changes in expression of collagenolytic/gelatinolytic enzymes of the matrix metalloproteinase family (MMP) in healing or ulcerating corneal wounds of rat or rabbit. Correlation of our findings with specific changes in the extracellular matrix of the repair tissue suggests two different roles for the enzymes, MMP-2 and MMP-9. MMP-2 is expressed in undamaged corneal stroma where it may degrade the occasional collagen molecule that becomes damaged. After corneal wounding, expression of this enzyme is increased and much of it appears in the active form. These changes persist for at least seven months, suggesting that MMP-2 is involved in the prolonged process of collagen remodelling in the stromal repair tissue. MMP-9 is expressed in the epithelial layer of repair tissue with a timing suggesting it might participate in controlling resynthesis of the basement membrane. MMP-9 also appears to be involved in degradation of the epithelial basement membrane that precedes corneal ulceration.
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PMID:Collagenolytic/gelatinolytic enzymes in corneal wound healing. 132 8

This study was performed to characterize the matrix metalloproteinases (MMPs) produced during the degradation of cotton-wrapped cartilage, implanted into the murine air pouch. One, two or three weeks following cartilage implantation, proteins were extracted from the granulation tissue and MMP activities were measured. Although collagenase-, gelatinase- and stromelysin-like activities were detected at each time point, gelatinase activity was by far the most prominent. These enzymes were inhibited by EDTA, but not by NEM or PMSF, indicating that these proteinases were metalloproteinases. Gelatin zymography revealed several lysis zones amongst which a major 92-kDa band shifted to 83- and 68-kDa species during the course of implantation. The emergence of these species coincided with enhanced gelatinolytic activity and collagen loss from the implanted cartilage.
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PMID:Gelatinase is the main matrix metalloproteinase involved in granuloma-induced cartilage degradation. 133 18

Vascular endothelial growth factor (VEGF) is a 45kDa secreted peptide that has potent mitogenic activity specific for endothelial cells in vitro and the ability to induce a strong angiogenic response in vivo. In the present study, 24 h treatment with VEGF resulted in a stimulation of expression of the metalloproteinase, interstitial collagenase, at the protein and mRNA levels 2.5-3.0-fold in human umbilical vein endothelial cells but not in human dermal fibroblasts. The dose response curve for collagenase induction was biphasic with the peak stimulatory response obtained by treatment of cells with 10-100 ng/ml (0.2-2 nM) VEGF. The dose response curve for collagenase induction overlapped with, but was not identical to, the response curve for proliferation, which showed VEGF mitogenic activity between < or = 0.1-50 ng/ml (< or = 0.002-1 nM). There was no induction seen in expression of other members of the matrix metalloproteinase family, including the 72kDa type IV collagenase, the 92kDa type V collagenase, or stromelysin. Expression of transcripts for the major metalloproteinase inhibitor, tissue inhibitor of metalloproteinases, was also unaltered by treatment with VEGF (1-200 ng/ml). These studies demonstrate that in addition to stimulating proliferation of endothelial cells, VEGF can also induce the expression of the only metalloproteinase that can initiate degradation of interstitial collagen types I-III under normal physiological conditions. Both responses are likely to contribute to the angiogenic potential of this peptide.
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PMID:Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. 144 17

The 72-kd type IV collagenase (matrix metalloproteinase-2 [MMP-2]) is a neutral metalloproteinase that initiates the degradation of type IV collagen in basement membranes. Its production by tumor cells has been correlated with the invasive and metastatic potential of neoplasms. Two recently developed affinity-purified antibodies against synthetic peptides from the amino terminus (H1) and an internal domain (Ab48) of the molecule were used to investigate immunohistochemically the distribution of this enzyme in a variety of thyroid tissues. All primary carcinomas (20 papillary, seven follicular, and three medullary) as well as nine of 11 metastases were positive, with the more aggressive tumors (tall cell variant of papillary carcinomas and invasive follicular carcinomas) tending to be more reactive than the low-grade tumors (classic and microinvasive papillary carcinomas and minimally invasive follicular tumors). Negative or minimal positivity was found in six cases of normal thyroid, one goiter, and two cases of Graves' disease. Immunoreactive follicular cells were seen focally in areas of inflammation, fibrosis, and distortion of normal follicles, and in Hashimoto's thyroiditis (four cases). Five of nine adenomas showed positive cells, but this could be related to previous trauma to the area. We conclude that there is increased production of the 72-kd type IV collagenase (MMP-2) in thyroid cancer; however, this enzyme also is elevated in benign conditions that are undergoing remodeling and repair.
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PMID:Distribution of the 72-kd type IV collagenase in nonneoplastic and neoplastic thyroid tissue. 146 77

We have documented changes in collagenolytic/gelatinolytic enzymes of the matrix metalloproteinase family (MMP) in remodelling rabbit cornea. MMP-2 (65 kDa gelatinase) in the proenzyme form is synthesized by the cells of the normal corneal stroma. After keratectomy the level of MMP-2 is increased in the stroma and enzyme appears in both pro- and activated forms. In addition, corneal cells synthesize MMP-9 (92 kDa gelatinase) in the proenzyme form after keratectomy; expression occurs in both the epithelial as well as stromal corneal layers. Changes in expression of both enzymes are precisely localized to the repairing portion of cornea, but demonstrate important differences in timing that correlate with the timing of specific events of matrix remodelling. Our data suggest that each of the gelatinases plays a different role in tissue remodelling after injury. We hypothesize that MMP-2 performs a surveillance function in normal cornea, catalyzing degradation of collagen molecules that occasionally become damaged. After wounding, this enzyme appears to participate in the prolonged process of collagen remodelling in the corneal stroma that eventually results in functional regeneration of the tissue. MMP-9 expression does not correlate with stromal remodelling, but we suggest that the enzyme might play a part in controlling resynthesis of the epithelial basement membrane.
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PMID:Differential roles for two gelatinolytic enzymes of the matrix metalloproteinase family in the remodelling cornea. 165 41

The matrix metalloproteinases (MMPs) collagenase, gelatinase and stromelysin, contribute to the destruction of articular cartilage which occurs during rheumatoid and osteoarthritis. Ro 31-4724, a substrate analogue containing a hydroxamic acid function, is a potent but non-selective inhibitor of all three MMPs (I50, collagenase = 10 nM), whereas Ro 31-7467, a phosphinic acid transition-state analogue, shows 14-fold and 12-fold selectivity for collagenase (I50 = 17 nM) over gelatinase and caseinase (stromelysin) respectively. The effects of these inhibitors on interleukin-1-induced bovine nasal cartilage degradation were examined. The hydroxamate Ro 31-4724 inhibits proteoglycan and collagen loss, whereas the phosphinic acid Ro 31-7467 selectively inhibits collagen breakdown in this model. This represents the first demonstration of potent and selective inhibition of IL1-induced cartilage degradation in vitro by MMP inhibitors. These results suggest that collagenase is responsible for collagen loss and that a different enzyme, possibly stromelysin, is responsible for proteoglycan degradation in this model.
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PMID:Potent collagenase inhibitors prevent interleukin-1-induced cartilage degradation in vitro. 166 94

The site of action of cysteine-proteinases (CPs) and matrix metalloproteinases (MMPs) in the degradation of bone collagen by osteoclasts was investigated by evaluating the effects of the CP-inhibitor trans-epoxy-succinyl-L-leucylamido (4-guanidino)-butane (E-64) and the MMP-inhibitor N-(3-N-benzyloxycarbonyl amino-1-R-carboxypropyl)-L-leucyl-O-methyl-L-tyrosine N-methylamide (Cl-1) in an in vitro model system of PTH-stimulated mouse calvaria. In the presence of each of the two inhibitors a large area of collagen free of mineral crystallites was seen adjacent to the ruffled border of the osteoclasts. Following a culture period of 24 h this area proved to be about 10 times larger in inhibitor-treated explants than in controls. Moreover the percentage of osteoclasts in close contact with such demineralized bone areas appeared to be significantly higher in inhibitor-treated explants than in control specimens (60% and 5%, respectively). These effects were not apparent when the osteoclastic activity was inhibited with calcitonin. No significant differences were found between the effects of the two inhibitors, E-64 and Cl-1. Our observations indicate that under the influence of inhibitors of MMPs and CPs demineralization of bone by osteoclasts proceeded up to a certain point whereas matrix degradation was strongly inhibited. It is concluded that within the osteoclastic resorption lacuna both CPs and MMPs participate in the degradation of the collagenous bone matrix.
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PMID:Degradation of collagen in the bone-resorbing compartment underlying the osteoclast involves both cysteine-proteinases and matrix metalloproteinases. 173 28

Articular cartilage contains at least five genetically distinct types of collagen. Types II, IX, and XI are cartilage-specific and are cross-linked together in a copolymeric network that forms the extracellular framework of the tissue. Fibrils of type II collagen provide the basic architecture. Type XI, a quantitatively minor fibril-forming collagen, is probably copolymerized with type II collagen in the matrix. Type IX collagen accounts for approximately 1% of the collagenous protein in adult articular cartilage and its molecules exist in the tissue covalently linked to the surface of type II collagen fibrils. Its suspected functions include regulating fibril diameters and mediating fibril-fibril and fibril-proteoglycan interactions. Stromelysin, a matrix metalloproteinase, was recently shown to degrade type IX collagen. This action may cause the collagen network swelling seen in articular cartilage in early experimental osteoarthritis, (OA). Collagen type X is restricted to the underlying calcified zone of articular cartilage, a zone that exhibits active remodeling in joints with OA. Degradation products of the various cartilage collagens show promise as molecular markers of joint disease.
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PMID:The collagens of articular cartilage. 179 2

Human articular cartilage released significantly increased levels of metal-dependent enzymes capable of degrading collagen, casein, and gelatin at a neutral pH following exposure to a sterile, purified fraction of Staphylococcus aureus culture medium. Neutral metalloprotease activity was determined by radiolabeled substrate assays and substrate gel analysis. The enzymes were activated with 4-aminophenylmercuric acetate and were inhibited by 1,10-phenanthroline and ethylenediamine tetraacetic acid. Protein immunoblots demonstrated that type I collagenase and stromelysin (matrix metalloproteinase III) secretion was increased following staphylococcal medium challenge. The profile of enzymatic activity induced by staphylococcal medium was directly comparable to that observed with interleukin-1, which was used as a positive control. The staphylococcal medium had no inherent proteolytic activity. Increased production of the neutral metalloproteases collagenase and stromelysin may significantly contribute to the extensive cartilage destruction noted in staphylococcal septic arthritis.
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PMID:Purified staphylococcal culture medium stimulates neutral metalloprotease secretion from human articular cartilage. 184 14


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