PubMed:15671273 JSONTXT

{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":112,"end":322},"obj":"OBJECTIVE"},{"id":"T2","span":{"begin":332,"end":967},"obj":"METHODS"},{"id":"T3","span":{"begin":977,"end":1516},"obj":"RESULTS"},{"id":"T4","span":{"begin":1530,"end":2101},"obj":"CONCLUSIONS"}],"text":"PAF-induced furin and MT1-MMP expression is independent of MMP-2 activation in corneal myofibroblasts.\nPURPOSE: Corneal stromal myofibroblasts express the platelet-activating factor (PAF) receptor, but its role is unclear. In the present study, the effect of PAF on induction of metalloproteinases (MMPs) was investigated.\nMETHODS: Rabbit corneal myofibroblasts were identified by immunodetection of alpha-smooth muscle (alpha-SM)-actin. MT1-MMP, MMP-2, MMP-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2 were detected by immunofluorescence. Cells were treated with 100 nM cPAF, with or without the PAF antagonist BN 50730 or the furin inhibitor nona-D-arg-NH(2). Gene-expression levels for furin, urokinase plasminogen activator, MMP-2, MMP-9, MT1-MMP, and TIMP-2 were determined by real-time PCR. Protein expression was assessed by Western blot. MMP-2 and -9 activity was determined by gelatin zymography. Active MT1-MMP levels were measured by ELISA.\nRESULTS: cPAF triggered significantly increased MT1-MMP, MMP-2, MMP-9, and TIMP-2 mRNA expression, followed by increased active MT1-MMP protein expression at 12 hours, whereas TIMP-2 protein increased at 24 hours. PAF also induced furin gene expression, followed by increased protein expression. Nona-D-arg-NH(2) blocked cPAF induction of MT1-MMP activity. PAF-treated myofibroblasts showed increased active MMP-9 protein, but unchanged MMP-2 activity. Pretreatment with BN 50730 blocked PAF-induced transcription and translation of these proteins.\nCONCLUSIONS: PAF, through a receptor-mediated mechanism, induces a specific pattern of furin, MMP, and TIMP-2 expression in corneal myofibroblasts. MMP-2 activity was unchanged by PAF treatment. These results suggest that in response to the inflammatory mediator PAF, induction of MT1-MMP is independent of MMP-2 activity in corneal myofibroblasts. Thus, PAF-mediated changes in extracellular matrix composition surrounding the myofibroblasts could be important in regulating the corneal scarring process. Moreover, PAF antagonists could be useful in maintaining corneal transparency."}

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furin and MT1-MMP expression is independent of MMP-2 activation in corneal myofibroblasts.\nPURPOSE: Corneal stromal myofibroblasts express the platelet-activating factor (PAF) receptor, but its role is unclear. In the present study, the effect of PAF on induction of metalloproteinases (MMPs) was investigated.\nMETHODS: Rabbit corneal myofibroblasts were identified by immunodetection of alpha-smooth muscle (alpha-SM)-actin. MT1-MMP, MMP-2, MMP-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2 were detected by immunofluorescence. Cells were treated with 100 nM cPAF, with or without the PAF antagonist BN 50730 or the furin inhibitor nona-D-arg-NH(2). Gene-expression levels for furin, urokinase plasminogen activator, MMP-2, MMP-9, MT1-MMP, and TIMP-2 were determined by real-time PCR. Protein expression was assessed by Western blot. MMP-2 and -9 activity was determined by gelatin zymography. Active MT1-MMP levels were measured by ELISA.\nRESULTS: cPAF triggered significantly increased MT1-MMP, MMP-2, MMP-9, and TIMP-2 mRNA expression, followed by increased active MT1-MMP protein expression at 12 hours, whereas TIMP-2 protein increased at 24 hours. PAF also induced furin gene expression, followed by increased protein expression. Nona-D-arg-NH(2) blocked cPAF induction of MT1-MMP activity. PAF-treated myofibroblasts showed increased active MMP-9 protein, but unchanged MMP-2 activity. Pretreatment with BN 50730 blocked PAF-induced transcription and translation of these proteins.\nCONCLUSIONS: PAF, through a receptor-mediated mechanism, induces a specific pattern of furin, MMP, and TIMP-2 expression in corneal myofibroblasts. MMP-2 activity was unchanged by PAF treatment. These results suggest that in response to the inflammatory mediator PAF, induction of MT1-MMP is independent of MMP-2 activity in corneal myofibroblasts. Thus, PAF-mediated changes in extracellular matrix composition surrounding the myofibroblasts could be important in regulating the corneal scarring process. Moreover, PAF antagonists could be useful in maintaining corneal transparency."}

{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":102},"obj":"DRI_Approach"},{"id":"T2","span":{"begin":112,"end":222},"obj":"DRI_Outcome"},{"id":"T3","span":{"begin":223,"end":322},"obj":"DRI_Background"},{"id":"T4","span":{"begin":332,"end":437},"obj":"DRI_Background"},{"id":"T5","span":{"begin":438,"end":555},"obj":"DRI_Background"},{"id":"T6","span":{"begin":556,"end":677},"obj":"DRI_Approach"},{"id":"T7","span":{"begin":678,"end":812},"obj":"DRI_Background"},{"id":"T8","span":{"begin":813,"end":861},"obj":"DRI_Background"},{"id":"T9","span":{"begin":862,"end":921},"obj":"DRI_Unspecified"},{"id":"T10","span":{"begin":922,"end":967},"obj":"DRI_Background"},{"id":"T11","span":{"begin":977,"end":1181},"obj":"DRI_Background"},{"id":"T12","span":{"begin":1182,"end":1263},"obj":"DRI_Background"},{"id":"T13","span":{"begin":1264,"end":1324},"obj":"DRI_Unspecified"},{"id":"T14","span":{"begin":1325,"end":1336},"obj":"REPLACED"},{"id":"T15","span":{"begin":1337,"end":1351},"obj":"Token_Label.OUTSIDE"},{"id":"T16","span":{"begin":1352,"end":1420},"obj":"DRI_Unspecified"},{"id":"T17","span":{"begin":1421,"end":1516},"obj":"DRI_Background"},{"id":"T18","span":{"begin":1530,"end":1664},"obj":"DRI_Approach"},{"id":"T19","span":{"begin":1665,"end":1711},"obj":"DRI_Unspecified"},{"id":"T20","span":{"begin":1712,"end":1865},"obj":"DRI_Challenge"},{"id":"T21","span":{"begin":1866,"end":2022},"obj":"DRI_Approach"},{"id":"T22","span":{"begin":2023,"end":2101},"obj":"DRI_Outcome"}],"text":"PAF-induced furin and MT1-MMP expression is independent of MMP-2 activation in corneal myofibroblasts.\nPURPOSE: Corneal stromal myofibroblasts express the platelet-activating factor (PAF) receptor, but its role is unclear. In the present study, the effect of PAF on induction of metalloproteinases (MMPs) was investigated.\nMETHODS: Rabbit corneal myofibroblasts were identified by immunodetection of alpha-smooth muscle (alpha-SM)-actin. MT1-MMP, MMP-2, MMP-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2 were detected by immunofluorescence. Cells were treated with 100 nM cPAF, with or without the PAF antagonist BN 50730 or the furin inhibitor nona-D-arg-NH(2). Gene-expression levels for furin, urokinase plasminogen activator, MMP-2, MMP-9, MT1-MMP, and TIMP-2 were determined by real-time PCR. Protein expression was assessed by Western blot. MMP-2 and -9 activity was determined by gelatin zymography. Active MT1-MMP levels were measured by ELISA.\nRESULTS: cPAF triggered significantly increased MT1-MMP, MMP-2, MMP-9, and TIMP-2 mRNA expression, followed by increased active MT1-MMP protein expression at 12 hours, whereas TIMP-2 protein increased at 24 hours. PAF also induced furin gene expression, followed by increased protein expression. Nona-D-arg-NH(2) blocked cPAF induction of MT1-MMP activity. PAF-treated myofibroblasts showed increased active MMP-9 protein, but unchanged MMP-2 activity. Pretreatment with BN 50730 blocked PAF-induced transcription and translation of these proteins.\nCONCLUSIONS: PAF, through a receptor-mediated mechanism, induces a specific pattern of furin, MMP, and TIMP-2 expression in corneal myofibroblasts. MMP-2 activity was unchanged by PAF treatment. These results suggest that in response to the inflammatory mediator PAF, induction of MT1-MMP is independent of MMP-2 activity in corneal myofibroblasts. Thus, PAF-mediated changes in extracellular matrix composition surrounding the myofibroblasts could be important in regulating the corneal scarring process. Moreover, PAF antagonists could be useful in maintaining corneal transparency."}