Antisense oligonucleotides for PDGF-B and its receptor inhibit mechanical strain-induced fetal lung cell growth

M. Liu, J. Liu, S. Buch, A. K. Tanswell, M. Post

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

An intermittent mechanical strain regimen, which simulates fetal breathing movements, has been shown to enhance DNA synthesis and cell division of fetal rat lung cells. The signaling mechanism through which the physical stimulus is transduced is unknown. Herein, we report that mechanical strain (5% elongation, 60 cycles/min) of fetal lung cells, cultured in a three- dimensional environment provided by Gelfoam sponges, increased the mRNA levels of platelet-derived growth factor B (PDGF-B) and β-receptor (PDGF- β-R) within 5 min of the onset of strain. Both PDGF-BB and PDGF-β-R proteins were increased after a 24-h intermittent strain (15 min/h). Phosphorothioate antisense PDGF-B oligonucleotides (ON) at 15 μM abolished the strain-enhanced DNA synthesis and cell growth. Scrambled PDGF-B ON had no such effect. A neutralizing PDGF-BB antibody (10 μg/ml) also attenuated strain-induced DNA synthesis. Furthermore, the strain-induced stimulatory effect on DNA synthesis of fetal tung cells was blocked by tyrphostin 9 (1 μM), a PDGF receptor-associated tyrosine kinase inhibitor, but not by its inactive structural analogue tyrphostin 1. Antisense but not sense PDGF-β-R ON (10 μM) also abrogated the strain-enhanced DNA synthesis. These results suggest that physical forces such as fetal breathing movements regulate fetal lung cell growth by controlling PDGF-B and PDGF-β-R gene expression.

Original languageEnglish (US)
Pages (from-to)L178-L184
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume269
Issue number2 13-2
DOIs
StatePublished - 1995

Keywords

  • gene expression
  • lung development
  • physical forces
  • platelet-derived growth factor
  • signal transduction

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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