title: Functional components of basic fibroblast growth factor signaling that inhibit lung elastin gene expression.
abstract: Previously, we have demonstrated that basic fibroblast growth factor (bFGF) decreases elastin gene transcription in confluent rat lung fibroblasts via the binding of a Fra-1-c-Jun heterodimer to an activator protein-1-cAMP response element in the distal region of the elastin promoter. In the present study, we show that bFGF activates the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2, resulting in the translocation of phosphorylated extracellular signal-regulated kinase 1/2 into the nucleus followed by increased binding of Elk-1 to the serum response element of the c-Fos promoter, transient induction of c-Fos mRNA, and sustained induction of Fra-1 mRNA. The addition of PD-98059, an inhibitor of mitogen-activated protein kinase kinase, abrogates the bFGF-dependent repression of elastin mRNA expression. Comparative analyses of confluent and subconfluent fibroblast cultures reveal significant differences in elastin mRNA levels and activator protein-1 protein factors involved in the regulation of elastin transcription. These findings suggest that bFGF modulates specific cellular events that are dependent on the state of the cell and provide a rationale for the differential responses that can be expected in development and injury or repair situations.
authors.forename: I
authors.initials: I
authors.lastname: Carreras
authors.forename: C B
authors.initials: CB
authors.lastname: Rich
authors.forename: J A
authors.initials: JA
authors.lastname: Jaworski
authors.forename: S J
authors.initials: SJ
authors.lastname: Dicamillo
authors.forename: M P
authors.initials: MP
authors.lastname: Panchenko
authors.forename: R
authors.initials: R
authors.lastname: Goldstein
authors.forename: J A
authors.initials: JA
authors.lastname: Foster
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins; D004549:Elastin / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000201:enzymology*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008168:Lung / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D050807:ets-Domain Protein Elk-1; D000099169:Fos-Related Antigen 1
chemical_list: D004268:DNA-Binding Proteins; D004549:Elastin; D004791:Enzyme Inhibitors; D016222:Fibroblast Growth Factor 2; D005419:Flavonoids; D020928:Mitogen-Activated Protein Kinases; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D000099169:Fos-Related Antigen 1; C494114:Elk1 protein, rat; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one