Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tenascin (TN) is a large oligomeric glycoprotein that is present transiently in the extracellular matrix (ECM) of cells and is involved in morphogenetic movements, tissue patterning, and tissue repair. It has multiple domains, both adhesive and anti-adhesive, that interact with cells and with fibronectin (FN) and other ECM macromolecules. We have studied the consequences of the interaction of TN with a FN matrix on gene expression in rabbit synovial fibroblasts. Fibroblasts plated on a mixed substrate of FN and TN, but not on FN alone, upregulated synthesis of four genes: collagenase, stromelysin, the 92-kDa gelatinase, and c-fos. Although the fibroblasts spread well on both FN and FN/TN substrates, nuclear c-Fos increased within 1 h only in cells that were plated on FN/TN. TN did not induce the expression of collagenase in cells plated on substrates of type I collagen or vitronectin (VN). Moreover, soluble TN added to cells adhering to a FN substrate or to serum proteins had no effect, suggesting that TN has an effect only in the context of mixed substrates of FN and TN. Collagenase increased within 4 h of plating on a FN/TN substrate and exhibited kinetics similar to those for induction of collagenase gene expression by signaling through the integrin FN receptor. Arg-Gly-Asp peptide ligands that recognize either the FN receptor or the VN receptor and function-perturbing anti-integrin monoclonal antibodies diminished the interaction of fibroblasts with a mixed substrate of FN, TN, and VN, but had no effect on the adhesion of fibroblasts to a substrate of FN and VN, suggesting that both receptors recognize the complex. Anti-TN68, an antibody that recognizes an epitope in the carboxyl-terminal type III repeats involved in the interaction of TN with both FN and cells, blocked the inductive effect of the FN/TN substrate, whereas anti-TNM1, an antibody that recognizes an epitope in the amino-terminal anti-adhesive region of epidermal growth factor-like repeats, had no effect. These data suggest that transient alteration of the composition of ECM by addition of proteins like TN may regulate the expression of genes involved in cell migration, tissue remodeling, and tissue invasion, in regions of tissue undergoing phenotypic changes.
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PMID:The extracellular matrix ligands fibronectin and tenascin collaborate in regulating collagenase gene expression in fibroblasts. 751 5

Immunohistochemical studies of prostate carcinoma reveal that most primary carcinomas, including high-grade tumors, are surrounded by a basal lamina composed of laminin, type IV collagen, and entactin. In addition to the expected laminin subchains A, B1, B2, subchains M and S are also found. Tenascin, found around normal glands, is seen in 60% of carcinomas. The basal cells of the normal gland express several integrin alpha units including alpha 2,3,4,5,6, and v. Both beta 1 and beta 4 subunits are observed. These integrin units are polarized at the base of the cells where they codistribute with the surrounding extracellular matrix. The integrin alpha 6 beta 4 is associated with hemidesmosomal-like structures, as detected by transmission electron microscopy (TEM). In carcinoma, the beta 4 is not observed and the alpha 6 and beta 1 subunits are variably expressed. The integrin expression in carcinoma is diffuse in the cytoplasmic membrane and not restricted to the basal aspects of the cell. In addition, type VII collagen and the BP 180 protein which are associated with hemidesmosomes are lost, although the BP 230, plectin, and HD1 proteins are variably expressed. Using immunohistochemistry and northern analysis we observed three metalloproteinases in prostate carcinoma--matrilysin, gelatinase A, and gelatinase B. Western blotting and zymogram analysis reveal that of these three, only matrilysin appears to be present in its active form. Recent in situ hybridization studies reveal focal expression of the matrilysin mRNA in 25/33 primary carcinomas. Matrilysin also appears to be highly expressed in prostatic ducts and atrophic glands. Expression of the three metalloproteinases is also seen in prostatic intraepithelial neoplasia lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adhesion molecules, extracellular matrix, and proteases in prostate carcinoma. 782 96

Glomerulopathic light chains (LCs) are associated with two distinct mesangiopathies: AL (light-chain-related) amyloidosis and light-chain deposition disease (LCDD) with immunomorphologic features that are well documented in the literature. Even though both conditions are caused by monoclonal LCs, these entities differ dramatically in their morphologic expressions. In AL amyloidosis the mesangial matrix is replaced by amyloid fibrils, while in LCDD the matrix increases as a consequence of deposition of excess extracellular matrix (ECM). The immunomorphologic mesangial alterations observed in biopsy material are closely reproduced in vitro when mesangial cells grown on an artificial matrix are incubated with monoclonal light chains obtained from the urine of patients with either condition. This article summarizes previously reported data, reports new findings, and focuses on integrating all the available information on the subject. When mesangial cells are incubated with LCDD-LCs, production of ECM proteins (collagen IV, laminin, fibronectin, and tenascin) is increased, with maximum effect at 72 hours post LC treatment. A concomitant decrease in collagenase IV activity further accentuates the accumulation of mesangial matrix. These effects are mediated through transforming growth factor-beta (TGF-beta) activation. In contrast, when mesangial cells are incubated with Am-LCs, a decrease in ECM protein production and a stimulatory effect on collagenase IV is observed, which results in matrix degradation and facilitates amyloid deposition. The decreased TGF-beta documented in the literature in this setting precludes adequate matrix repair. These findings substantiate the morphologic alterations observed in renal biopsy specimens and in the in vitro model. Using this in vitro model, it is then possible to delineate the LC interactions with putative receptors at the mesangial cell surface that regulate mesangial cell pathobiologic responses and mesangial matrix homeostasis.
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PMID:Glomerulopathic light chain-mesangial cell interactions modulate in vitro extracellular matrix remodeling and reproduce mesangiopathic findings documented in vivo. 1036 4

In patients with sudden unexpected cardiac death, there is a relationship between the interstitial fibrosis of the myocardium and matrix molecules with a role in global remodeling of the cardiac stroma. Tissue samples of left ventricular myocardium from 17 middle-aged patients with sudden cardiac death, following acute or chronic ischemic cardio(myo)pathies, were analyzed using standard HE stain and the indirect tristadial ABC peroxidase immunohistochemical method for a panel of four antibodies involved in the dynamic remodeling of extracellular matrix: matrix metalloproteinase 9 (MMP9), tenascin X (Tn-X), TGF-b, CD54 (ICAM-1), together with simultaneously assessment of troponin in myocardic fibers. The most sensitive reaction was noticed for ICAM-1 in 71% of cases, followed by MMP9 in 59% of cases and TGF-b in 47% of cases (with great specificity for capillary vessels), in the extracellular matrix of the residual cardiomyocytes. A direct correlation, statistically significant was recorded between troponin and MMP9 (r = 0.65, p = 0.01), troponin and ICAM-1 (r = 0.31, p = 0.02), respectively ICAM-1 and tenascin (r = 0.72, p = 0.01). The extensive expression of ICAM-1 in the extracellular matrix from the perilesional area probably plays a role in the stimulation of new developing adhesion substrates between residual cells and adjacent stroma, while the over expression of troponin in the residual cardiomyocytes is accompanied by a high expression of MMP9 in the myocardic interstitium, with heterogeneous remodeling of the ventricular stroma. The simultaneous IHC expression of tenascin and ICAM-1 suggests a colocalization required for the nerve sprouting in the residual myocardium and for developing new focal cell-matrix adhesion contacts.
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PMID:Simultaneous immunophenotypical assessment of troponin and extracellular matrix molecules in myocardium of patients with sudden cardiac death. 1922 53