Endothelial and Serum Factors Which Include Apolipoprotein A1 Tether Elastin to Smooth Muscle Cells Inducing Serine Elastase Activity Via Tyrosine Kinase-Mediated Transcription and Translation

Karen Thompson, Jun Kobayashi, Tim Childs, Dennis Wigle, Marlene Rabinovitch

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

We previously reported that serine elastase activity is induced in cultured porcine pulmonary artery (PA) smooth muscle cells (SMC) following serum stimulation by a mechanism involving adhesion of elastin to an elastin binding protein and tyrosine kinase activity. The present study demonstrates that a PA endothelial cell factor also promotes a fourfold increase in elastin adhesion to PA SMC and a twofold increase in serine elastase activity. The mechanism involves tethering of the factor to SMC, since [3H]-elastin pre-incubated with serum or endothelial cell (EC)-conditioned medium or SMC pre-treated with serum accelerates binding of elastin and tyrosine-kinase related elastase activity. The serum factor appears to interact with integrins as elastase induction is partially inhibited by RGD peptides. The elastase-inducing properties of serum could not, however, be attributed to several RGD-containing proteins. While a 120 kD fibronectin fragment partially reproduced the effect, it was not found in the serum fraction containing elastase-inducing activity. Instead, a 27 kD serum protein was enriched by elastin affinity chromatography, identified as apolipoprotein (Apo) A1 by microsequence analysis, and found to have about 50% of the elastase-inducing activity of serum. Elastase induction is inhibited by actinomycin and cycloheximide, suggesting a requirement for mRNA transcription and protein synthesis. Our results suggest a novel cell-extracellular matrix interaction whereby a soluble factor, in this case a lipoprotein, binds and tethers a matrix component to the cell surface and induces tyrosine kinase-dependent transcription of mRNA culminating in substrate proteolysis.

Original languageEnglish (US)
Pages (from-to)78-89
Number of pages12
JournalJournal of Cellular Physiology
Volume174
Issue number1
DOIs
StatePublished - Jan 1998

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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