Serine proteinase inhibitors influence the stability of
tropoelastin mrna in neonatal rat lung fibroblast cultures.
McGowan, Stephen E., Rugao Liu, Catherine S. Harvey, and Elise C.
Jaeckel.
Department of Veterans Affairs Research Service and the University
of Iowa College of Medicine
APStracts 2:0212L, 1995.
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 (LF) 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.
Received 15 March 1995; accepted in final form 29 September 1995.
APS Manuscript Number L83-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95