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

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

Research output: Contribution to journalArticle

77 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume269
Issue number2 13-2
StatePublished - Jan 1 1995

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Proto-Oncogene Proteins c-sis
platelet-derived growth factor
Antisense Oligonucleotides
oligonucleotides
cell growth
lungs
Lung
receptors
Oligonucleotides
DNA
Growth
Fetal Movement
synthesis
Respiration
Aleurites
Tyrphostins
Absorbable Gelatin Sponge
vpr Genes
Platelet-Derived Growth Factor Receptors
breathing

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine
  • Agricultural and Biological Sciences(all)

Cite this

Antisense oligonucleotides for PDGF-B and its receptor inhibit mechanical strain-induced fetal lung cell growth. / Liu, M.; Liu, J.; Buch, Shilpa J; Tanswell, A. K.; Post, M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 269, No. 2 13-2, 01.01.1995.

Research output: Contribution to journalArticle

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