Exogenous and endogenous transforming growth factors-beta influence elastin gene expression in cultured lung fibroblasts

Stephen E McGowan; Sheila K Jackson; Paula J Olson; Trilok Parekh; Leslie I Gold

doi:10.1165/ajrcmb.17.1.2686

Back

Exogenous and endogenous transforming growth factors-beta influence elastin gene expression in cultured lung fibroblasts

Journal article

Peer reviewed

Exogenous and endogenous transforming growth factors-beta influence elastin gene expression in cultured lung fibroblasts

Stephen E McGowan, Sheila K Jackson, Paula J Olson, Trilok Parekh and Leslie I Gold

American journal of respiratory cell and molecular biology, Vol.17(1), pp.25-35

07/1997

DOI: 10.1165/ajrcmb.17.1.2686

PMID: 9224206

View Online

Abstract

Elastin, an important structural protein of the extracellular matrix, confers elastic properties on the pulmonary alveolar interstitium. In the alveolar wall, elastin is primarily produced postnatally by fibroblasts. The mechanisms that regulate lung fibroblast (LF) elastin gene expression have not been completely defined, although both transcriptional and posttranscriptional mechanisms appear to be involved. Transforming growth factors-beta (TGF-beta s) have been shown to increase elastin production by cultured neonatal rat LF. Analyses of elastin gene transcription and mRNA stability indicate that exogenous TGF-beta 1 increases the half-life of tropoelastin mRNA by 1.5-fold and does not alter elastin gene transcription. Interference with the functions of endogenous TGF-beta 1 in cultured LF, through the addition of neutralizing antibodies or antisense oligodeoxynucleotides, decreases tropoelastin and tropoelastin mRNA production by these cells. The content of total (latent plus active) TGF-beta s was approximately 4.5-fold greater in lungs obtained from rats on postnatal day 8 than in lungs obtained from adults. These findings indicate that endogenous TGF-beta s, in cultured LF, regulate elastin gene expression, most likely by a posttranscriptional mechanism. Since others have shown that elastin mRNA appears to have a longer half-life in neonatal than in adult rat lungs, we hypothesize that the higher content of TGF-beta s could contribute to the greater elastin mRNA stability in neonatal lungs.

Transfection

Cell Line

Promoter Regions, Genetic

Transcription, Genetic - drug effects

Oligonucleotides, Antisense - pharmacology

Humans

Cells, Cultured

Transforming Growth Factor beta - physiology

Rats

Recombinant Proteins - biosynthesis

RNA, Messenger - metabolism

Rats, Sprague-Dawley

Tropoelastin - biosynthesis

Antibodies - pharmacology

Transforming Growth Factor beta - pharmacology

Animals

Transforming Growth Factor beta - genetics

Fibroblasts - drug effects

Lung - drug effects

Elastin - biosynthesis

Female

Lung - metabolism

Mink

Fibroblasts - metabolism

Details

Title: Subtitle: Exogenous and endogenous transforming growth factors-beta influence elastin gene expression in cultured lung fibroblasts
Creators: Stephen E McGowan - Department of Veterans Affairs Research Service, Washington, District of Columbia, USA
Sheila K Jackson
Paula J Olson
Trilok Parekh
Leslie I Gold
Resource Type: Journal article
Publication Details: American journal of respiratory cell and molecular biology, Vol.17(1), pp.25-35
DOI: 10.1165/ajrcmb.17.1.2686
PMID: 9224206
NLM abbreviation: Am J Respir Cell Mol Biol
ISSN: 1044-1549
eISSN: 1535-4989
Publisher: United States
Grant note: HL45135 / NHLBI NIH HHS
Language: English
Date published: 07/1997
Academic Unit: International Programs; Internal Medicine
Record Identifier: 9983983660602771

Metrics

19 Record Views

56 Times Cited - Web of Science