Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To explore the role of the matrix metalloproteinase matrilysin (MAT) in normal tissue remodeling, we cloned the murine homologue of MAT from postpartum uterus using RACE polymerase chain reaction and examined its pattern of expression in embryonic, neonatal, and adult mice. The murine coding sequence and the corresponding predicted protein sequence were found to be 75% and 70% identical to the human sequences, respectively, and organization of the six exons comprising the gene is similar to the human gene. Northern analysis and in situ hybridization revealed that MAT is expressed in the normal cycling, pregnant, and postpartum uterus, with levels of expression highest in the involuting uterus at early time points (6 h to 1.5 days postpartum). The mRNA was confined to epithelial cells lining the lumen and some glandular structures. High constitutive levels of MAT transcripts were also detected in the small intestine, where expression was localized to the epithelial Paneth cells at the base of the crypts. Similarly, MAT expression was found in epithelial cells of the efferent ducts, in the initial segment and cauda of the epididymis, and in an extra-hepatic branch of the bile duct. MAT transcripts were detectable only by reverse transcription-polymerase chain reaction in the colon, kidney, lung, skeletal muscle, skin, stomach, juvenile uterus, and normal, lactating, and involuting mammary gland, as was expression primarily late in embryogenesis. Analysis of MAT expression during postnatal development indicated that although MAT is expressed in the juvenile small intestine and reproductive organs, the accumulation of significant levels of MAT mRNA appears to correlate with organ maturation. These results show that MAT expression is restricted to specific organs in the mouse, where the mRNA is produced exclusively by epithelial cells, and suggest that in addition to matrix degradation and remodeling, MAT may play an important role in the differentiated function of these organs.
Mol Biol Cell 1995 Jul
PMID:The metalloproteinase matrilysin is preferentially expressed by epithelial cells in a tissue-restricted pattern in the mouse. 757 99

Matrilysin, which is a member of the matrix metalloproteinase family and is implicated in colon cancer invasion, is expressed in human colon adenocarcinoma-derived SW1116 cells. We investigated the effect of alpha-difluoromethylornithine (DFMO) on matrilysin expression in this cell line because others have shown that DFMO can inhibit invasion and carcinogenesis in epithelial tissues, including the colon, in experimental models. DFMO reduced extracellular levels of matrilysin protein after 4 d of treatment. Intracellular levels of matrilysin protein were minimally affected by DFMO treatment. The decrease in extracellular matrilysin protein levels caused by DFMO was not a consequence of lowered steady-state levels of matrilysin mRNA. After 4 d of exposure, the amount of this transcript was higher in DFMO-treated cells than in untreated cultures, whereas the mRNA stabilities were similar. These data show that polyamine depletion by DFMO can suppress the expression of matrilysin, a gene product thought to be involved in tumor invasion. The decrease in extracellular matrilysin protein caused by DFMO treatment appears to be due to a posttranscriptional mechanism, although transcription of this gene also seems to be affected by polyamines in SW1116 cells.
Mol Carcinog 1994 Nov
PMID:Polyamine-dependent expression of the matrix metalloproteinase matrilysin in a human colon cancer-derived cell line. 794 2

Myocardial fibrosis is associated with an activated renin-angiotensin-aldosterone system (RAAS). In renovascular hypertension, this presents as a reactive perivascular and interstitial fibrosis in not only the pressure overloaded, hypertrophied left ventricle but also the normotensive, nonhypertrophied right ventricle. It therefore would appear that circulating hormonal and not hemodynamic factors are responsible for this adverse fibrous tissue response. To ascertain whether the RAAS effector hormones angiotensin II (AII) or aldosterone (ALDO) directly stimulate collagen synthesis or inhibit collagenase production we used cell culture. Adult rat cardiac fibroblasts (Fb) were cultured since these cells express mRNA for types I and III collagens, the major fibrillar collagens in the heart, and collagenase or matrix metalloproteinase 1 (MMP 1), the key enzyme for interstitial collagen degradation. Collagen synthesis, determined by 3H-proline incorporation, and collagenase activity were measured in confluent, quiescent Fb after 24 h incubation with various concentrations of AII or ALDO (10(-11)-10(-6)M) in the presence or absence of either 10(-5)M type 1 (DuP 753) and type 2 (PD 123177) AII or 10(-9)-3 x 10(-6)M ALDO (spironolactone) receptor antagonists, respectively. Collagen synthesis, normalized per total protein synthesis, increased significantly (P < 0.005) after incubation with either 10(-9)M ALDO (5.9 +/- 1.0%) or 10(-7)M AII (5.3 +/- 1.2%) compared with untreated control cells (2.9 +/- 0.5%) of the same passage (p6-p10). This increase in collagen synthesis could be completely abolished by either types 1 or 2 AII receptor antagonists in AII stimulated Fb or the competitive ALDO receptor antagonist, spironolactone, at equimolar concentration in ALDO stimulated Fb. AII significantly decreased collagenase activity which could be completely abolished by PD 123177, but not DuP 753, while ALDO had no effect on collagenase activity. The mineralocorticoid, ALDO, stimulates collagen synthesis in cultured adult rat cardiac Fb in concentrations similar to those found in plasma in renovascular hypertension and this response appears to occur via type I corticoid receptors. AII appears to stimulate collagen synthesis by both type 1 and 2 AII receptors, but only in high concentrations that could be generated locally within the myocardium. In addition, AII unlike ALDO inhibits collagenase activity that could be attenuated only by type 2 receptor blockade. These findings suggest a direct interaction between ALDO, AII and cardiac Fb in mediating myocardial fibrosis in hypertensive heart disease.
J Mol Cell Cardiol 1994 Jul
PMID:Collagen metabolism in cultured adult rat cardiac fibroblasts: response to angiotensin II and aldosterone. 796 49

The metalloproteinase matrilysin is widely expressed in the epithelial tumor cells of malignant colorectal adenocarcinomas. Approximately 50% of benign adenomas also express low levels of matrilysin that is focally localized. The expression of stromelysin-1, stromelysin-3, and gelatinase A was observed in the stromal component of several carcinomas and was not present in adenomatous tissue. The expression of interstitial collagenase and gelatinase B was observed in occasional adenomas and carcinomas. Stromelysin-2 transcripts were not detectable in any of the samples examined. Tissue inhibitor of metalloproteinase-1 gene expression was widespread and was observed in both epithelial and stromal cells of adenomas and carcinomas. These results indicate that matrilysin gene expression is an early event in colorectal tumorigenesis and that the expression of stromelysin-1, stromelysin-3, and gelatinase A is primarily a late event. The observed gene expression patterns suggest that matrilysin may participate in early events in tumor progression and that multiple members of the metalloproteinase family may work in concert to facilitate late-stage tumor invasion and metastasis.
Mol Carcinog 1994 Aug
PMID:Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis. 806 80

The metalloproteinases, a multigene family of metal-requiring enzymes, have been suggested to play a role in tumor invasion and metastasis. Previously, we demonstrated that human primary prostate tumors express higher levels of matrilysin and gelatinase A mRNA than normal prostate does. In the study presented here, we used in situ hybridization and immunohistochemical staining of serial sections of paraffin-embedded primary prostate tumors to compare the sites of matrilysin and gelatinase A expression and protein localization. These results confirmed the epithelial nature of matrilysin expression and protein localization. In contrast, gelatinase A mRNA was localized to the interstitial stroma, whereas the protein was associated with the epithelial tumor cells. In situ hybridization was also used to demonstrate that gelatinase B expression was restricted to macrophages infiltrating the tumors. Proteins isolated from an additional set of frozen tumor specimens were analyzed by western blotting to determine the relative amounts of matrilysin in the active and proenzyme forms. The western analyses demonstrated that in all cases in which matrilysin was detected, at least some of the enzyme was in the active form. These results are discussed with respect to the possible role these enzymes may play in prostate tumor progression.
Mol Carcinog 1996 Jan
PMID:Matrilysin expression in human prostate carcinoma. 856 67

The objective of the present analyses was to determine whether matrix metalloproteinases interact with alpha 2HS glycoprotein, the human homologue of bovine fetuin. Alpha 2HS glycoprotein was incubated with metalloproteinases at 1:1 and 1:10 molar ratios. The serum glycoprotein was completely degraded by gelatinase-A and matrilysin at the higher enzyme concentration after an overnight incubation at 37 degrees C. The data show that gelatinase-A, matrilysin and gelatinase-B do interact with alpha 2HS glycoprotein and that gelatinase-B associates most tightly with the serum glycoprotein.
Biochem Mol Biol Int 1996 Sep
PMID:The interactions of alpha 2HS glycoprotein with metalloproteinases. 888 65

Granulosa cells were prepared from follicular aspirates obtained at oocyte collection for in-vitro fertilization (IVF) and maintained in culture. Substantial loss of cells from the culture surface occurred in the absence of gonadotrophin when cells were maintained on a thin layer of extracellular matrix (ECM) using a defined, serum-free medium. This cell loss was clearly and significantly reduced in the presence of human chorionic gonadotrophin (HCG) by days 4-6 of culture, and occurred in conjunction with loss of ECM. Analysis of culture medium by zymography using gelatin as substrate demonstrated the presence of metalloproteinases (MMP), MMP-9 (gelatinase B) appearing as the predominant band. Measurement of overall gelatinase activity in culture media revealed a progressive fall in gelatinase expressed on a per cell basis in media from HCG-treated cultures and this was less marked in controls. This suppression of gelatinase activity was consistent with an observed increase in production of tissue inhibitor of metalloproteinase-1 (TIMP-1) by HCG-treated cells, which was significant by days 6-8 of culture. We speculate that stabilization of the ECM may be an important aspect of HCG action in the corpus luteum.
Mol Hum Reprod 1996 Jan
PMID:Effect of gonadotrophin on cell and matrix retention and expression of metalloproteinases and their inhibitor in cultured human granulosa cells modelling corpus luteum function. 923 53

We examined the expression of matrilysin mRNA in sporadic and hereditary colorectal adenomas to clarify the role of matrilysin in tumorigenesis. Matrilysin mRNA was not detected in normal colorectal mucosa from patients with either sporadic or familial adenomas. Matrilysin mRNA expression in sporadic adenomas correlated with the degree of dysplasia and the size of the mass, whereas most of the adenomas in patients with familial adenomatous polyposis coli expressed matrilysin mRNA irrespective of adenoma size or degree of dysplasia. Because matrilysin is more likely to be expressed in adenomas with a potential for malignancy, this enzyme may play a role in the malignant conversion of colorectal adenomas.
Mol Carcinog 1997 Aug
PMID:Matrilysin gene expression in sporadic and familial colorectal adenomas. 929 Jun 98

The spatial expression of mRNA for matrix metalloproteinase 2 (MMP-2), its putative activator, the membrane-type 1 matrix metalloproteinase (MT1-MMP), and the MMP-2 substrate type IV collagen was investigated in human placentas of both normal and tubal ectopic pregnancies and in cyclic endometrium using in-situ hybridization. Cytokeratin staining applied to adjacent sections was used to identify epithelial and trophoblast cells. In both normal and tubal pregnancies MT1-MMP, MMP-2 and type IV collagen mRNA were highly expressed and co-localized in the extravillous cytotrophoblasts of anchoring villi, in cytotrophoblasts that had penatrated into the placental bed and in cytotrophoblastic cell islands. In addition, the decidual cells of normal pregnancies in some areas co-expressed MT1-MMP and MMP-2 mRNA, with moderate signals for both components. Fibroblast-like stromal cells in tubal pregnancies were positive for MMP-2 mRNA but generally negative for MT1-MMP mRNA. The consistent co-localization of MT1-MMP with MMP-2 and type IV collagen in the same subset of cytotrophoblasts strongly suggests that all three components co-operate in the tightly regulated fetal invasion process. The co-expression of MT1-MMP and MMP-2 mRNA in some of the decidual cells indicates that these cells are also actively involved in the placentation process.
Mol Hum Reprod 1997 Aug
PMID:Co-ordinated expression of MMP-2 and its putative activator, MT1-MMP, in human placentation. 929 57

p53, a tumor suppressor and a transcription factor, has been shown to transcriptionally activate the expression of a number of important genes involved in the regulation of cell growth, DNA damage, angiogenesis, and apoptosis. In a computer search for other potential p53 target genes, we identified a perfect p53 binding site in the promoter of the human type IV collagenase (also called 72-kDa gelatinase or matrix metalloproteinase 2 [MMP-2]) gene. This p53 binding site was found to specifically bind to p53 protein in a gel shift assay. Transcription assays with luciferase reporters driven by the promoter or enhancer of the type IV collagenase gene revealed that (i) activation of the promoter activity is p53 binding site dependent in p53-positive cells but not in p53-negative cells and (ii) wild-type p53, but not p53 mutants commonly found in human cancers, transactivates luciferase expression driven by the type IV collagenase promoter as well as by a p53 site-containing enhancer element in the promoter. Significantly, expression of the endogenous type IV collagenase is also under the control of p53. Treatment of U2-OS cells, a wild-type p53-containing osteogenic sarcoma line, with a common p53 inducer, etoposide, induced p53 DNA binding and transactivation activities in a time-dependent manner. Induction of type IV collagenase expression followed the p53 activation pattern. No induction of type IV collagenase expression can be detected under the same experimental conditions in p53-negative Saos-2 cells. All these in vitro and in vivo assays strongly suggest that the type IV collagenase gene is a p53 target gene and that its expression is subject to p53 regulation. Our finding links p53 to a member of the MMP genes, a family of genes implicated in trophoblast implantation, wound healing, angiogenesis, arthritis, and tumor cell invasion. p53 may regulate these processes by upregulating expression of type IV collagenase.
Mol Cell Biol 1997 Nov
PMID:Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter. 934 94


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