SERINE PROTEINASE-INHIBITORS INFLUENCE THE STABILITY OF TROPOELASTIN MESSENGER-RNA IN NEONATAL RAT LUNG FIBROBLAST-CULTURES

Elastin, an elastic extracellular structural protein, is a polymer com prised of soluble tropoelastin (TE) monomers that are joined by covale nt cross-links and become insoluble. In cultured vascular smooth muscl e cells, the steady-state level of TE mRNA is influenced by soluble el astin moieties in the culture medium, either TE or its fragmentation p roducts. We have hypothesized that an enzyme-mediated proteolytic even t may modulate the quantities of TE and its fragmentation products in the culture medium of mesenchymal cells, and thereby indirectly regula te the steady-state level of TE mRNA. Neonatal rat lung fibroblasts we re cultured in the presence or absence of the serine proteinase inhibi tor, aprotinin, and the quantities of soluble elastin and TE mRNA were analyzed. Exposures to aprotinin lasting up to 12 h increased the sol uble elastin content of the culture medium. The increase in the solubl e elastin content did not reflect an increase in TE mRNA, which dimini shed after exposures for 12 h or longer. The decrease in TE mRNA resul ted from a decrease in its half-life, rather than a decrease in the ra te of TE gene transcription. Aprotinin did not reduce TE mRNA in plasm inogen-depleted cultures, but the effect of aprotinin was evident when purified plasminogen was added back to the cultures. Therefore, a ser ine proteinase, possibly plasmin, may participate in a feedback mechan ism and modulate the quantity of TE in lung fibroblast cultures. This mechanism may help ensure that intracellular TE synthesis occurs in ta ndem with extracellular elastin deposition and cross-linking.