Serine proteinase inhibitors influence the stability of tropoelastin mRNA in neonatal rat lung fibroblast cultures

Stephen E McGowan; Rugao Liu; Catherine S Harvey; Elise C Jaeckel

doi:10.1152/ajplung.1996.270.3.L376

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Serine proteinase inhibitors influence the stability of tropoelastin mRNA in neonatal rat lung fibroblast cultures

Journal article

Peer reviewed

Serine proteinase inhibitors influence the stability of tropoelastin mRNA in neonatal rat lung fibroblast cultures

Stephen E McGowan, Rugao Liu, Catherine S Harvey and Elise C Jaeckel

The American journal of physiology, Vol.270(3 Pt 1), pp.L376-L385

03/1996

DOI: 10.1152/ajplung.1996.270.3.L376

PMID: 8638730

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Abstract

Elastin, an elastic extracellular structural protein, is a polymer comprised of soluble tropoelastin (TE) monomers that are joined by covalent cross-links and become insoluble. In cultured vascular smooth muscle cells, the steady-state level of TE mRNA is influenced by soluble elastin moieties in the culture medium, either TE or its fragmentation products. We have hypothesized that an enzyme-mediated proteolytic event may modulate the quantities of TE and its fragmentation products in the culture medium of mesenchymal cells, and thereby indirectly regulate the steady-state level of TE mRNA. Neonatal rat lung fibroblasts were cultured in the presence or absence of the serine proteinase inhibitor, aprotinin, and the quantities of soluble elastin and TE mRNA were analyzed. Exposures to aprotinin lasting up to 12 h increased the soluble elastin content of the culture medium. The increase in the soluble elastin content did not reflect an increase in TE mRNA, which diminished after exposures for 12 h or longer. The decrease in TE mRNA resulted from a decrease in its half-life, rather than a decrease in the rate of TE gene transcription. Aprotinin did not reduce TE mRNA in plasminogen-depleted cultures, but the effect of aprotinin was evident when purified plasminogen was added back to the cultures. Therefore, a serine proteinase, possibly plasmin, may participate in a feedback mechanism and modulate the quantity of TE in lung fibroblast cultures. This mechanism may help ensure that intracellular TE synthesis occurs in tandem with extracellular elastin deposition and cross-linking.

Transcription, Genetic - drug effects

Protein Biosynthesis

Lung - cytology

RNA, Messenger - metabolism

Aprotinin - pharmacology

Time Factors

Lung - metabolism

Serine Proteinase Inhibitors - pharmacology

Fibroblasts - metabolism

RNA, Messenger - drug effects

Animals, Newborn

Fibrinolysin

Enzyme-Linked Immunosorbent Assay

Cells, Cultured

Rats

Rats, Sprague-Dawley

Tropoelastin - biosynthesis

Gene Expression Regulation - drug effects

Peptide Fragments - analysis

Blotting, Northern

Animals

Fibroblasts - drug effects

Elastin - biosynthesis

Fibroblasts - cytology

Kinetics

Details

Title: Subtitle: Serine proteinase inhibitors influence the stability of tropoelastin mRNA in neonatal rat lung fibroblast cultures
Creators: Stephen E McGowan - Department of Veterans Affairs Research Service, Iowa City, Iowa 52242, USA
Rugao Liu
Catherine S Harvey
Elise C Jaeckel
Resource Type: Journal article
Publication Details: The American journal of physiology, Vol.270(3 Pt 1), pp.L376-L385
DOI: 10.1152/ajplung.1996.270.3.L376
PMID: 8638730
NLM abbreviation: Am J Physiol
ISSN: 0002-9513
eISSN: 2163-5773
Publisher: American Physiological Society; United States
Grant note: R01-HL-45125 / NHLBI NIH HHS
Language: English
Date published: 03/1996
Academic Unit: International Programs; Internal Medicine
Record Identifier: 9983983644502771

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