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http://purl.uniprot.org/citations/17099140http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17099140http://www.w3.org/2000/01/rdf-schema#comment"Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD). Recent reports of increased matrix metalloproteinase-2 (MMP-2) in lungs of patients with emphysema support the paradigm of proteinase/antiproteinase imbalance in the pathogenesis of COPD. We sought to define the signaling pathways activated by smoke and to identify molecules responsible for emphysema-associated MMP-2 expression. In this study, we show that cigarette smoke extract (CSE) induced MMP-2 protein expression and increased MMP-2 gelatinase activity of normal lung fibroblasts. We previously identified a transcription factor, early growth response 1 (EGR-1), with robust expression in the lung tissues of patients with COPD compared with control smokers. Here, the treatment of fibroblasts with CSE resulted in marked induction of EGR-1 mRNA and protein in a dose- and time-dependent manner, accompanied by increased EGR-1 binding activity. CSE-induced MMP-2 mRNA and protein expression and activity were significantly inhibited using EGR-1 small interfering RNA (siRNA) or in Egr-1-null(-/-) mouse fibroblasts. Furthermore, we observed induction of membrane type 1 matrix metalloproteinase (MT1-MMP), which has an EGR-1-binding site on its promoter, in CSE-treated primary normal lung fibroblasts. The concomitant MT1-MMP expression and MMP-2 activation by CSE are inhibited by EGR-1 siRNA. Rapid activation of mitogen-activated protein kinases was observed in CSE-treated fibroblasts. Chemical inhibitors of ERK1/2 MAPK, but not of p38 and JNK, decreased CSE-induced EGR-1 protein expression and MMP-2 activity of fibroblasts. The identification that induction of MMP-2 and MT1-MMP by CSE from lung fibroblasts is EGR-1-dependent reveals a molecular mechanism for matrix remodeling in cigarette smoke-related emphysema."xsd:string
http://purl.uniprot.org/citations/17099140http://purl.org/dc/terms/identifier"doi:10.1165/rcmb.2006-0106oc"xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/author"Dong Y."xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/author"Li C."xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/author"Sun J."xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/author"Matthay M.A."xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/author"Ning W."xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/author"Choi A.M."xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/author"Feghali-Bostwick C.A."xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/name"Am J Respir Cell Mol Biol"xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/pages"480-490"xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/title"Cigarette smoke stimulates matrix metalloproteinase-2 activity via EGR-1 in human lung fibroblasts."xsd:string
http://purl.uniprot.org/citations/17099140http://purl.uniprot.org/core/volume"36"xsd:string
http://purl.uniprot.org/citations/17099140http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/17099140
http://purl.uniprot.org/citations/17099140http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/17099140
http://purl.uniprot.org/uniprot/#_A0A089VKS7-mappedCitation-17099140http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17099140
http://purl.uniprot.org/uniprot/#_B4DVG0-mappedCitation-17099140http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17099140
http://purl.uniprot.org/uniprot/#_B2R6P3-mappedCitation-17099140http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17099140
http://purl.uniprot.org/uniprot/#_B4DNX4-mappedCitation-17099140http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17099140
http://purl.uniprot.org/uniprot/#_K4RH61-mappedCitation-17099140http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17099140
http://purl.uniprot.org/uniprot/#_P08253-mappedCitation-17099140http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17099140
http://purl.uniprot.org/uniprot/#_P50281-mappedCitation-17099140http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17099140
http://purl.uniprot.org/uniprot/#_Q2EF79-mappedCitation-17099140http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17099140