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Michael W. Lark - One of the best experts on this subject based on the ideXlab platform.
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Induction of increased levels of proteoglycan fragments in synovial fluid (SF) and increased levels of Stromelysin in cartilage, synovium and SF by intraarticular injection of canine monocyte conditioned medium into dogs.
The Journal of rheumatology, 1994Co-Authors: Michael W. Lark, S A Donatelli, Joseph Mcdonnell, L. A. Hoerrner, Karla Stevens, C. A. Saphos, E K Bayne, N I Hutchinson, Vernon L. MooreAbstract:OBJECTIVE: To study the effects of the intraarticular injection of canine monocyte conditioned medium (cMCM) into dogs on proteoglycan fragment and Stromelysin levels in the joint. METHODS: cMCM was injected intraarticularly into dogs, and the levels of proteoglycan fragments in synovial fluid (SF) as well as Stromelysin levels in cartilage, synovium, and SF were assessed after 12 h. RESULTS: There was a 4-fold increase of proteoglycan fragment levels and a 6-fold increase in Stromelysin levels in SF, and a 4.4-fold increase in Stromelysin levels in cartilage extracts. Elevated mRNA levels were detected in both synovium and cartilage. By immunofluorescence staining, Stromelysin was localized in chondrocytes throughout the cartilage and in synovial cells. CONCLUSION: Intraarticular injection of cMCM stimulated the expression of Stromelysin mRNA and protein in cartilage and synovium and caused marked increases in Stromelysin protein and proteoglycan fragment levels in SF.
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metalloproteinases tissue inhibitor and proteoglycan fragments in knee synovial fluid in human osteoarthritis
Arthritis & Rheumatism, 1993Co-Authors: Stefan L Lohmander, L. A. Hoerrner, Michael W. LarkAbstract:Objective. To determine the concentrations of human Stromelysin-1, collagenase, tissue inhibitor of metalloproteinases (TIMP), and proteoglycan fragments in knee synovial fluid in patients with injury to the meniscus or anterior cruciate ligament, posttraumatic osteoarthritis, primary osteoarthritis, or pyrophosphate arthritis. Methods. Synovial fluid samples were collected from patients with knee disease diagnosed arthroscopically and radiologically. Concentrations of Stromelysin-1, collagenase, and TIMP-1 were determined by sandwich immunoassay, using monoclonal and polyclonal antibodies. Fragments of cartilage proteoglycan containing the chondroitin sulfate-binding region were determined by immunoassay with a polyclonal antibody. Results. Average concentrations of metalloproteinases, TIMP, and proteoglycan fragments in joint fluid were significantly elevated in patients from all disease groups as compared with volunteers with healthy knees (reference group). Stromelysin concentrations in disease groups averaged 15-45 times that of the reference group. The molar ratios between Stromelysin and collagenase varied between 10 and 150. The molar ratio between total Stromelysin and free TIMP was 0.5 in the reference group and between 1.6 and 5.3 in the disease groups. Conclusion. Stromelysin concentration in joint fluid is a parameter that distinguishes diseased joints from healthy joints, with a sensitivity of 84% and a specificity of 90%. The high concentrations of metalloproteinase relative to TIMP in joint fluid from patients with the conditions studied may be associated with cartilage matrix degradation in these arthritides. (Less)
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In vivo expression of Stromelysin in synovium and cartilage of rabbits injected intraarticularly with interleukin‐1β
Arthritis and rheumatism, 1992Co-Authors: Nancy I. Hutchinson, Michael W. Lark, Joseph Mcdonnell, L. A. Hoerrner, Vernon L. Moore, Karen L. Macnaul, Coral F. Harper, Susan Donatelli, E K BayneAbstract:Objective. To examine the in vivo expression of the matrix metalloproteinase Stromelysin in the synovium and articular cartilage of rabbits injected intraarticularly with recombinant human interleukin-1β (IL-1). Methods. The direct isolation of messenger RNA (mRNA) from articular cartilage without the prior isolation of chondrocytes is described. The in vivo expression of Stromelysin was examined at the mRNA level by Northern blot analysis, and at the protein level by in situ immunolocalization and by enzyme-linked immunosorbent assay. Results. In the synovium of IL-1–injected joints, Stromelysin mRNA levels were highest at 4 hours and declined to background levels within 24 hours. In the cartilage of IL-1–injected joints, Stromelysin mRNA was elevated at 4 hours and continued to increase until 8 hours, before declining. Stromelysin mRNA expression preceded a similar increase in Stromelysin protein levels in both synovium and cartilage. Conclusion. Intraarticular injection of IL-1 induced the endogenous expression of Stromelysin mRNA and protein in both synovium and cartilage. The kinetics of Stromelysin expression correlated well with the accumulation of Stromelysin and proteoglycan in synovial fluids. Therefore, the de novo synthesis of Stromelysin in cartilage may have contributed to the loss of proteoglycan from that tissue.
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detection of Stromelysin and collagenase in synovial fluid from patients with rheumatoid arthritis and posttraumatic knee injury
Arthritis & Rheumatism, 1992Co-Authors: Lori A Walakovits, Michael W. Lark, Vernon L. Moore, Nina Bhardwaj, Gregory S GallickAbstract:Objective. To quantify Stromelysin and collagenase in synovial fluid (SF) from patients with rheumatoid arthritis (RA) or traumatic knee injury. Methods. Stromelysin and collagenase were measured in the SF of 33 patients with RA or posttraumatic knee injury, using specific double-antibody sandwich enzyme-linked immunosorbent assays. Stromelysin was fractionated from representative SF, and the molecular form was identified by immunoblot analysis. Results. The Stromelysin concentration was ˜20-fold higher than the collagenase concentration in the fluids from patients with RA and ˜8-fold higher in the fluids from patients with traumatic injury. For both metalloproteinases, there was a higher enzyme concentration in RA SF than in the SF from patients with trauma (Stromelysin 40.1 ± 26 μ/ml [mean ± SD] in RA SF, 8.5 ± 15 μ/ml in trauma SF; collagenase 2.2 ± 3.3 μ/ml in RA SF, 1.1 ± 2.3 μ/ml in trauma SF). The majority of the Stromelysin within the SF bound to reactive red—agarose and was identified as proStromelysin based on electrophoretic mobility and immunoblotting with monospecific antibodies. Conclusion. The finding of high levels of Stromelysin in SF from patients with RA supports the proposal that this enzyme may play a role in the connective tissue degradation observed in this disease.
Ulpu Saarialho-kere - One of the best experts on this subject based on the ideXlab platform.
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Metalloelastase (MMP-12) and 92-kDa gelatinase (MMP-9) as well as their inhibitors, TIMP-1 and -3, are expressed in psoriatic lesions.
Experimental dermatology, 2001Co-Authors: Sari Suomela, Arja-leena Kariniemi, Erna Snellman, Ulpu Saarialho-kereAbstract:In skin biology, matrix metalloproteinases (MMPs) have been implicated in inflammatory matrix remodeling, neovascularization, wound healing and malignant transformation. Psoriasis is histologically characterized by keratinocyte hyperproliferation, infiltration of inflammatory cells, neoangiogenesis and production of cytokines, such as TNF-alpha, IL-1beta, TGF-alpha, and IFN-gamma, also capable of regulating MMP transcription. To investigate the role of Stromelysins-1 and -2, matrilysin, metalloelastase, collagenases-1 and -3 and 92-kDa gelatinase as well as their inhibitors, TIMPs-1 and -3, in psoriasis, we performed in situ hybridization using 35S-labeled cRNA probes on 29 psoriatic lesions and 9 samples of normal looking skin from psoriatic patients. Metalloelastase mRNA was detected in 21/27 samples in macrophages that had migrated into the epidermis or in the inflammatory infiltrates of the superficial dermis. A quantity of 92-kDa gelatinase was found in macrophages and neutrophils (25/27). Stromelysin-1 mRNA was detected in basal keratinocytes in 4/21 lesions. Intracellular laminin-5 immunosignal in basal keratinocytes of the same samples, suggested that Stromelysin-1 might participate in remodeling of the basement membrane zone. No signal for Stromelysin-2 or collagenase-3 was found and only sweat glands were positive for matrilysin. TIMP-1 was more abundantly expressed than TIMP-3 in the inflammatory infiltrates and endothelial cells of dermal papillae (22/29). TIMP-3 was expressed perivascularly in 9/16 samples. Our results suggest that overexpression of the investigated MMPs by keratinocytes is not associated with psoriasis. However, macrophages express MMPs in psoriatic skin. Also TIMPs, particularly TIMP-1, were abundantly expressed, suggesting that mere MMP overexpression is unlikely to contribute to psoriatic tissue changes.
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Stromelysin-2 is Upregulated During Normal Wound Repair and is Induced by Cytokines
The Journal of investigative dermatology, 2000Co-Authors: Oona Rechardt, Outi Elomaa, M Vaalamo, Kati Pääkkönen, Tiina Jahkola, Johanna Höök-nikanne, Rosalind M. Hembry, Lari Häkkinen, Juha Kere, Ulpu Saarialho-kereAbstract:Stromelysin-2 is a matrix metalloproteinase that degrades in vitro several protein components relevant to wound repair such as collagens III and IV, gelatin, nidogen, laminin-1, proteoglycans, and elastin. Furthermore, it can activate other matrix metalloproteinases, such as collagenase-1 (matrix metalloproteinase-1) and collagenase-2 (matrix metalloproteinase-8), as well as 92 kDa gelatinase. The aim of this study was to determine in a large variety of wounds (normally healing dermal and mucosal wounds, suction blisters, ex vivo cultures, diabetic, decubitus, rheumatic, and venous ulcers) and keratinocyte cultures, which factors contribute to Stromelysin-2 expression and how it is induced in relation to other matrix metalloproteinases. Our results show that Stromelysin-2 mRNA and protein are upregulated later (at 3 d) than matrix metalloproteinase-1 in normally healing wounds and ex vivo explants, in which Stromelysin-2 is invariably expressed by keratinocytes migrating over dermal matrix. The number of keratinocytes expressing Stromelysin-2 was greatest in chronic inflamed diabetic and venous ulcers compared with rheumatoid and decubitus ulcers, six of which had no signal. In keratinocyte cultures, tumor necrosis factor-α, epidermal growth factor, and transforming growth factor-β1 induced Stromelysin-2 expression as measured by quantitative reverse transcriptase–polymerase chain reaction, whereas different matrices did not upregulate the mRNA. Immunostaining demonstrated stromal transforming growth factor-β1 in contact with the Stromelysin-2-positive keratinocytes. Our results suggest that Stromelysin-2 expression is important for the normal repair process and is upregulated by cytokines rather than cell–matrix interactions. Stromelysin-2 is most likely to participate in the remodeling of the newly formed basement membrane, and is not overexpressed in retarded wound healing.
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Distinct populations of basal keratinocytes express Stromelysin-1 and Stromelysin-2 in chronic wounds.
The Journal of clinical investigation, 1994Co-Authors: Ulpu Saarialho-kere, William C. Parks, Alice P. Pentland, Henning Birkedal-hansen, Howard G WelgusAbstract:Wound repair involves cell migration and tissue remodeling, and these ordered and regulated processes are facilitated by matrix-degrading proteases. We reported that interstitial collagenase is invariantly expressed by basal keratinocytes at the migrating front of healing epidermis (Saarialho-Kere, U. K., E. S. Chang, H. G. Welgus, and W. C. Parks, 1992. J. Clin. Invest. 90:1952-1957). Because of the limited substrate specificity of collagenase, principally for interstitial fibrillar collagens, other enzymes must also be produced in the wound environment to effectively restructure tissues with a complex matrix composition. Stromelysins-1 and -2 are closely related, yet distinct metalloproteinases, and both can degrade many noncollagenous connective tissue macromolecules. Using in situ hybridization and immunohistochemistry, we found that both Stromelysins are produced by distinct populations of keratinocytes in a variety of chronic ulcers. Stromelysin-1 mRNA and protein were detected in basal keratinocytes adjacent to but distal from the wound edge in what probably represents the sites of proliferating epidermis. In contrast, Stromelysin-2 mRNA was seen only in basal keratinocytes at the migrating front, in the same epidermal cell population that expresses collagenase. Stromelysin-1-producing keratinocytes resided on the basement membrane, whereas Stromelysin-2-producing keratinocytes were in contact with the dermal matrix. Furthermore, Stromelysin-1 expression was prominent in dermal fibroblasts, whereas no signal for Stromelysin-2 was seen in any dermal cell. These findings demonstrate that Stromelysins-1 and -2 are produced by different populations of basal keratinocytes in response to wounding and suggest that these two matrix metalloproteinases serve distinct roles in tissue repair.
Sabine Werner - One of the best experts on this subject based on the ideXlab platform.
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Activities of the Matrix Metalloproteinase Stromelysin-2 (MMP-10) in Matrix Degradation and Keratinocyte Organization in Wounded Skin
Molecular biology of the cell, 2004Co-Authors: Monika Krampert, Wilhelm Bloch, Takako Sasaki, Philippe Bugnon, Thomas Rülicke, Eckhard Wolf, Monique Aumailley, William C. Parks, Sabine WernerAbstract:The matrix metalloproteinase Stromelysin-2 is expressed in keratinocytes of the epithelial tongue of skin wounds, suggesting a role in keratinocyte migration. Here, we show that Stromelysin-2 enhances migration of cultured keratinocytes. To gain insight into the in vivo activities of Stromelysin-2 in epithelial repair, we generated transgenic mice expressing a constitutively active Stromelysin-2 mutant in keratinocytes. These animals had no alterations in skin architecture, and the healing rate of skin wounds was normal. Histologically, however, we found abnormalities in the organization of the wound epithelium. Keratinocytes at the migrating epidermal tip were scattered in most sections of mice with high expression level, and there was a reduced deposition of new matrix. In particular, the staining pattern of laminin-5 at the wound site was altered. This may be due to proteolytic processing of laminin-5 by Stromelysin-2, because degradation of laminin-5 by this enzyme was observed in vitro. The inappropriate matrix contact of keratinocytes was accompanied by aberrant localization of β1-integrins and phosphorylated focal adhesion kinase, as well as by increased apoptosis of wound keratinocytes. These results suggest that a tightly regulated expression level of Stromelysin-2 is required for limited matrix degradation at the wound site, thereby controlling keratinocyte migration.
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cDNA cloning and expression of the gene encoding murine Stromelysin-2 (MMP-10).
Gene, 1997Co-Authors: Marianne Madlener, Sabine WernerAbstract:Recently, we demonstrated a biphasic induction of the epithelial broad-spectrum matrix metalloproteinase (MMP) Stromelysin-2 during cutaneous wound healing. Now we have generated a murine wound cDNA libary and have used it to isolate the putative cDNA of this murine matrix metalloproteinase. The predicted sequence of the protein shows 76 and 89% identity with its human and rat analogues, respectively. Stromelysin-2 and Stromelysin-1 transcripts were both detected at very low levels in the lung and the heart of adult Balb/c mice, whereas Stromelysin-2 mRNA expression alone was found at comparatively high levels in the small intestine, a tissue characterized by continuous epithelial renewal. Recombinant forms of murine Stromelysin-1 and -2 produced in transfected COS cells were secreted and could be induced to undergo autocatalytic processing by addition of the organomercurial salt 4-aminophenylmercuric acetate (APMA).
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Regulation of the expression of Stromelysin-2 by growth factors in keratinocytes: implications for normal and impaired wound healing
Biochemical Journal, 1996Co-Authors: Marianne Madlener, William C. Parks, Cornelia Mauch, Walter Conca, Maria Brauchle, Sabine WernerAbstract:Keratinocyte growth factor (KGF) has been implicated in wound re-epithelialization and branching morphogenesis of several organs. To determine whether KGF induces these effects via induction of matrix metalloproteinase expression we have analysed the effect of KGF on the expression of Stromelysin-2 in cultured HaCaT keratinocytes. Here we show a strong induction of Stromelysin-2 mRNA within 5-8 h of stimulation of these cells with KGF. The degree of induction was similar to that achieved by treatment with epidermal growth factor or tumour necrosis factor alpha, whereas the stimulatory effect of transforming growth factor beta 1 was even stronger. To determine whether the induction of Stromelysin-2 expression by growth factors and cytokines might be important for wound healing, we analysed the expression of this gene during the healing process of full-thickness excisional wounds in mice. Whereas Stromelysin-2 mRNA could hardly be detected in unwounded skin, a biphasic induction was seen after injury and highest levels were found at days 1 and 5 after wounding. Hybridization in situ revealed the presence of Stromelysin-2 mRNA in basal keratinocytes at the wound edge but not in the underlying mesenchymal tissue. During impaired wound healing as seen in glucocorticoid-treated mice, Stromelysin-2 expression was significantly increased compared with untreated control mice. Taken together, these results suggest that correct regulation of this broad-spectrum metalloproteinase might be important for normal repair.
Paul Basset - One of the best experts on this subject based on the ideXlab platform.
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Stromelysin-3 Is Induced in Mouse Ovarian Follicles Undergoing Hormonally Controlled Apoptosis, but This Metalloproteinase Is Not Required for Follicular Atresia
Biology of Reproduction, 2001Co-Authors: Anna-carin Hägglund, Paul Basset, Tor NyAbstract:Apoptotic processes are often associated with an intense proteolytic remodeling of the extracellular matrix (ECM). Proteolytic degradation of the ECM can also be a signal that induces apoptosis. Here, we have investigated the expression pattern and functional role of the matrix metalloproteinase Stromelysin-3 in follicular atresia. Twenty-four hours after the treatment of immature female mice with a low dose of eCG, both apoptosis and the Stromelysin-3 mRNA expression were suppressed approximately threefold. However, the initial suppression of apoptosis and Stromelysin-3 expression was followed by a time-dependent increase, and 96 h after eCG treatment, the levels were similar to those of untreated control mice. In 15- to 16-day-old juvenile mice, the ovary consisted of relatively undeveloped follicles, and almost no apoptosis and only low Stromelysin-3 mRNA expression were observed. However, at the age of 21 days, when several antral follicles were present, a fivefold induction in both apoptosis and Stromelysin-3 mRNA expression was detected. For both models, in situ analysis revealed that the expression of Stromelysin-3 mRNA was localized to the granulosa cells of atretic follicles. To address the functional role of Stromelysin-3 in follicular atresia, Stromelysin-3-deficient mice were studied. However, no difference in the pattern of apoptotic DNA fragmentation and no apparent morphological differences were observed when ovaries from wild-type and Stromelysin-3-deficient mice were compared. Taken together, our data indicate that Stromelysin-3 is induced during follicular atresia, but that this protease is not obligatory for initiation or completion of the atretic process.
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expression of Stromelysin 3 in atherosclerotic lesions regulation via cd40 cd40 ligand signaling in vitro and in vivo
Journal of Experimental Medicine, 1999Co-Authors: Uwe Schonbeck, Ethan Levesque, Michael P Herman, Pierre Graber, Galina K Sukhova, Elizabeth Atkinson, Paul Basset, Francois Mach, Peter LibbyAbstract:Stromelysin-3 is an unusual matrix metalloproteinase, being released in the active rather than zymogen form and having a distinct substrate specificity, targeting serine proteinase inhibitors (serpins), which regulate cellular functions involved in atherosclerosis. We report here that human atherosclerotic plaques ( n = 7) express Stromelysin-3 in situ, whereas fatty streaks ( n = 5) and normal arterial specimens ( n = 5) contain little or no Stromelysin-3. Stromelysin-3 mRNA and protein colocalized with endothelial cells, smooth muscle cells, and macrophages within the lesion. In vitro, usual inducers of matrix metalloproteinases such as interleukin-1, interferon-γ, or tumor necrosis factor α did not augment Stromelysin-3 in vascular wall cells. However, T cell–derived as well as recombinant CD40 ligand (CD40L, CD154), an inflammatory mediator recently localized in atheroma, induced de novo synthesis of Stromelysin-3. In addition, Stromelysin-3 mRNA and protein colocalized with CD40L and CD40 within atheroma. In accordance with the in situ and in vitro data obtained with human material, interruption of the CD40–CD40L signaling pathway in low density lipoprotein receptor–deficient hyperlipidemic mice substantially decreased expression of the enzyme within atherosclerotic plaques. These observations establish the expression of the unusual matrix metalloproteinase Stromelysin-3 in human atherosclerotic lesions and implicate CD40–CD40L signaling in its regulation, thus providing a possible new pathway that triggers complications within atherosclerotic lesions.
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Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo
Journal of Experimental Medicine, 1999Co-Authors: Uwe Schonbeck, Michael P Herman, Pierre Graber, Ethan B. Levesque, Galina K Sukhova, Elizabeth Atkinson, Paul Basset, Francois Mach, Peter LibbyAbstract:Stromelysin-3 is an unusual matrix metalloproteinase, being released in the active rather than zymogen form and having a distinct substrate specificity, targeting serine proteinase inhibitors (serpins), which regulate cellular functions involved in atherosclerosis. We report here that human atherosclerotic plaques ( n = 7) express Stromelysin-3 in situ, whereas fatty streaks ( n = 5) and normal arterial specimens ( n = 5) contain little or no Stromelysin-3. Stromelysin-3 mRNA and protein colocalized with endothelial cells, smooth muscle cells, and macrophages within the lesion. In vitro, usual inducers of matrix metalloproteinases such as interleukin-1, interferon-γ, or tumor necrosis factor α did not augment Stromelysin-3 in vascular wall cells. However, T cell–derived as well as recombinant CD40 ligand (CD40L, CD154), an inflammatory mediator recently localized in atheroma, induced de novo synthesis of Stromelysin-3. In addition, Stromelysin-3 mRNA and protein colocalized with CD40L and CD40 within atheroma. In accordance with the in situ and in vitro data obtained with human material, interruption of the CD40–CD40L signaling pathway in low density lipoprotein receptor–deficient hyperlipidemic mice substantially decreased expression of the enzyme within atherosclerotic plaques. These observations establish the expression of the unusual matrix metalloproteinase Stromelysin-3 in human atherosclerotic lesions and implicate CD40–CD40L signaling in its regulation, thus providing a possible new pathway that triggers complications within atherosclerotic lesions.
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the 28 kda n terminal domain of mouse Stromelysin 3 has the general properties of a weak metalloproteinase
Journal of Biological Chemistry, 1993Co-Authors: Gillian Murphy, J. P. Segain, Olivier Lefebvre, Mark I Cockett, Mark Oshea, C. Ioannou, Pierre Chambon, Paul BassetAbstract:Abstract The putative matrix metalloproteinase mouse Stromelysin-3 was expressed from Escherichia coli and from a mouse myeloma cell line. In the former case a single major protein of 58-kDa was detectable by immunoblotting, but no proteolytic activity could be elicited by zymography or trypsin or organomercurial treatment as would be expected for a typical matrix metalloproteinase. In the latter case immunodetectable proteins of 55-58 and 27-28-kDa were produced. The effect of trypsin or organomercurial treatment of the 55-58-kDa forms was to generate a 51-kDa form and lower molecular mass fragments. Upon zymographic analysis only the 27-28-kDa forms showed caseinolytic activity. N-terminal sequencing and immunoblotting analysis with antibodies specific to distinct domains of Stromelysin-3 indicated that the 27-28-Da Stromelysin-3 forms had lost the predicted propeptide and the majority of the C-terminal domain. The purified 28-kDa form of Stromelysin-3 could weakly degrade a number of extracellular matrix proteins and was inhibited by TIMP. However, the evidence that mature full-length Stromelysin-3 is a metalloproteinase could not be substantiated and the precise role of this protein in vivo remains to be elucidated. By partial analogy with interstitial collagenase, one hypothesis is that Stromelysin-3 with an intact C-terminal domain has specific properties for an as yet undefined substrate.
Lynn M Matrisian - One of the best experts on this subject based on the ideXlab platform.
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Non-human primate models: artificial menstrual cycles, endometrial matrix metalloproteinases and s.c. endometrial grafts
Human Reproduction, 1996Co-Authors: Robert Brenner, Lynn M Matrisian, L. Rudolph, Ov D. SlaydenAbstract:Rhesus monkeys are useful models in which to examine the hormonal regulation of endometrial matrix metalloproteinases (MMP) and to evaluate the role of MMP in uterine bleeding. Artificial 28 day menstrual cycles can be induced in ovariectomized monkeys by inserting an oestradiol implant for 2 weeks, then inserting a progesterone implant for 2 weeks, and then, with the oestradiol implant remaining in place, removing and reinserting the progesterone implant at 2 week intervals. To examine MMP during menses, we established such cycles and removed uteri by hysterectomy at closely spaced intervals before, during and after menses, as well as at later time points. Some samples were also obtained during menses induced by the withdrawal of both progesterone and oestradiol. We examined mRNA of the following MMP by Northern blotting: matrilysin, Stromelysin-1, Stromelysin-2, Stromelysin-3 and the tissue inhibitor of MMP TIMP-1. The expression of these MMP mRNA increased substantially by 2-3 days after progesterone withdrawal, whether or not oestradiol was maintained. The expression of some of the MMP (Stromelysins-1 and -2) returned very rapidly to baseline levels by 5 days after progesterone withdrawal, while the expression of others (matrilysin, Stromelysin-3 and TIMP-1) declined more slowly, reaching a baseline level by 10 days after progesterone withdrawal, with little or no further decline after progesterone concentrations rose during the induced luteal phase. Immunocytochemical studies showed that matrilysin was expressed primarily in the glands of the upper functionalis. In other work with the rhesus monkey model, we used a s.c. endometrial autograft technique in which pieces of endometrium were autotransplanted to the abdominal skin. During menses in the grafts, matrilysin was expressed in the glands of the grafts similar to the glands in the eutopic endometrium. Endometrial autografts can serve as a useful model for the study of MMP in uterine bleeding.
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Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis.
Molecular carcinogenesis, 1994Co-Authors: Ken J. Newell, Jean P Witty, William H. Rodgers, Lynn M MatrisianAbstract: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 collage-nase 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. © 1994 Wiley-Liss, Inc.
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The role of C-Fos in growth factor regulation of Stromelysin/transin gene expression.
Matrix (Stuttgart Germany). Supplement, 1992Co-Authors: Lynn M MatrisianAbstract:Expression of the rat Stromelysin (transin) gene is stimulated by growth factors such as epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), and inhibited by transforming growth factor-beta (TGF beta). Stimulation by both EGF and PDGF requires the presence of factors that recognize the AP-1 binding site in the Stromelysin promoter, but PDGF stimulation requires induction of the protooncogene c-fos, while EGF acts through a FOS-independent pathway. The FOS-independent pathway appears to involve protein kinase C (PKC), since EGF, but not PDGF, requires activated protein kinase C to stimulate Stromelysin expression. TGF beta inhibition of Stromelysin gene expression requires an upstream sequence, referred to as the TGF beta inhibitory element (TIE). FOS is also a part of a protein complex that binds to the TIE. The protooncogene FOS is therefore involved in both stimulation and inhibition of Stromelysin gene expression.
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The Role of the Matrix Metalloproteinase Stromelysin in the Progression of Squamous Cell Carcinomas
The American journal of the medical sciences, 1991Co-Authors: Lynn M Matrisian, Susan Mcdonnell, Donna B. Miller, Marc Navre, Elisabeth A. Seftor, Mary J.c. HendrixAbstract:The expression of the metalloproteinase Stromelysin correlates with the progression of chemically induced squamous cell carcinomas. We demonstrate that the expression of activated Stromelysin in papilloma-derived cells enhances in vitro cell invasion. We also demonstrate that the Ha-ras oncogene induces the transcription of the Stromelysin gene through an AP-1 dependent pathway. The hypothesis is that alterations in oncogenes and suppressor genes influence Stromelysin expression and thus influence subsequent steps of tumor invasion and metastasis.
