Transcriptional regulation of pulmonary elastin gene expression in elastase-induced injury

Author:

Rich Celeste B.1,Carreras Isabel1,Lucey Edgar C.1,Jaworski Julie A.1,Buczek-Thomas Jo Ann1,Nugent Matthew A.1,Stone Phillip1,Foster Judith Ann1

Affiliation:

1. Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118

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.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

Reference44 articles.

1. Albin RJ, Senior RM, Welgus HG, Connolly NL, and Campbell EJ. Metalloproteinase elastase inhibition by human alveolar macrophages. In: Pulmonary Emphysema and Proteolysis. Part V, edited by Taylor JC and Mittman C. Orlando, FL: Academic, 1986, p. 283–288.

2. Basic fibroblast growth factor decreases elastin production by neonatal rat lung fibroblasts.

3. Developmental Changes in Tropoelastin mRNA Levels in Rat Lung: Evaluation byIn SituHybridization

4. Elastase-mediated Release of Heparan Sulfate Proteoglycans from Pulmonary Fibroblast Cultures

5. Heparan sulfate depletion within pulmonary fibroblasts: Implications for elastogenesis and repair

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