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dc.contributor.authorReunanen, N.zh_CN
dc.contributor.authorLi, S. P.zh_CN
dc.contributor.authorAhonen, M.zh_CN
dc.contributor.authorFoschi, M.zh_CN
dc.contributor.authorHan, J. H.zh_CN
dc.contributor.authorKahari, V. M.zh_CN
dc.contributor.author韩家淮zh_CN
dc.date.accessioned2013-12-12T02:24:43Z
dc.date.available2013-12-12T02:24:43Z
dc.date.issued2002zh_CN
dc.identifier.citationJournal of Biological Chemistry,277(35):32360-32368zh_CN
dc.identifier.issn0021-9258zh_CN
dc.identifier.otherISI:000177718700132zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/65811
dc.description.abstractHere, we have examined the role of distinct MAPK pathways in the regulation of collagenase-1 (matrix metalloproteinase (MMP)-1) and stromelysin-1 (MMP-3) expression by human skin fibroblasts. Tumor necrosis factor-alpha rapidly and transiently activated ERK1/2 and JNK in fibroblasts, whereas the activation of p38 MAPK was more persistent. Inhibition of p38 activity by SB203580 markedly (by 80-90%) inhibited induction of MMP-1 and MMP-3 expression by tumor necrosis factor-alpha, whereas blocking the activation of ERK1/2 by PD98059 had no effect. Activation of endogenous ERK1/2 by adenovirus-mediated transfer of constitutively active MEK1 resulted in potent induction of MMP-1 and MMP-3 expression. Activation of endogenous or adenovirally expressed p38alpha by adenovirally delivered constitutively active MKK3b and MKK6b also enhanced MMP-1 and MMP-3 expression and augmented the up-regulatory effect of ERK1/2 activation on the expression of these MMPs. Activation of ERK1/2 resulted in induction of c-jun, junB, and c-fos expression, whereas activation of p38 alone had no effect. In contrast, activation of p38alpha resulted in marked stabilization of MMP-1 and MMP-3 mRNAs. These results identify two distinct and complementary signaling mechanisms mediating induction of MMP-1 and MMP-3 expression in dermal fibroblasts: AP-1-dependent transcriptional activation via the ERK1/2 pathway and AP-1-independent enhancement via p38alpha MAPK by mRNA stabilization. It is conceivable that both modes of action play an important role in controlling the proteolytic phenotype of fibroblasts, e.g. in wound repair and tumor invasion.zh_CN
dc.language.isoen_USzh_CN
dc.subjectHUMAN FIBROBLAST COLLAGENASEzh_CN
dc.subjectMESSENGER-RNA STABILITYzh_CN
dc.subjectHUMAN SKIN FIBROBLASTSzh_CN
dc.subjectPROTEIN-KINASEzh_CN
dc.subjectGENE-EXPRESSIONzh_CN
dc.subjectI COLLAGENzh_CN
dc.subject3-DIMENSIONAL COLLAGENzh_CN
dc.subjectGROWTH-FACTORzh_CN
dc.subjectP38zh_CN
dc.subjectCELLSzh_CN
dc.titleActivation of p38 alpha MAPK enhances collagenase-1 (Matrix metalloproteinase (MMP)-1) and stromelysin-1 (MMP-3) expression by mRNA stabilizationzh_CN
dc.typeArticlezh_CN


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