title: Transcriptional regulation of pulmonary elastin gene expression in elastase-induced injury.
abstract: Previously we have shown that treatment of confluent, pulmonary fibroblast cultures with elastase results in upregulation of elastin mRNA and protein levels. In the present study we focused on determining the level at which elastin expression is upregulated after elastase exposure. We examined as models for this investigation elastin gene expression in primary pulmonary fibroblast cells during the transition from subconfluent to confluent cultures and in confluent, matrix-laden cultures treated briefly with elastase. In addition, we extended our studies to mice that were given an intratracheal dose of elastase; the effects on lung elastin mRNA and elastin promoter activity levels were measured and compared with results from in vitro cell models. The results demonstrate that upregulation of elastin gene expression during the transition of subconfluent to confluent cultures and after elastase injury is associated with an increase in the level of transcription both in vitro and in vivo. Furthermore, intratracheal administration of elastase to transgenic mice illustrates that the increased levels of elastin mRNA are accompanied by increased activity of the elastin gene promoter in cells spatially positioned near major sites of tissue injury.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Celeste B
authors.initials: CB
authors.lastname: Rich
authors.forename: Isabel
authors.initials: I
authors.lastname: Carreras
authors.forename: Edgar C
authors.initials: EC
authors.lastname: Lucey
authors.forename: Julie A
authors.initials: JA
authors.lastname: Jaworski
authors.forename: Jo Ann
authors.initials: JA
authors.lastname: Buczek-Thomas
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Nugent
authors.forename: Phillip
authors.initials: P
authors.lastname: Stone
authors.forename: Judith Ann
authors.initials: JA
authors.lastname: Foster
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004549:Elastin / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D010196:Pancreatic Elastase / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D004549:Elastin; D010196:Pancreatic Elastase