Antisense oligonucleotides against pdgf-b and its receptor inhibit mechanical strain-induced fetal lung cell growth. Liu, Mingyao, Jason Liu, Shilpa Buch, A. Keith Tanswell, Martin Post. The Medical Research Council Group in Lung Development and the Neonatal Research Division, Hospital for Sick Children Research Institute, Department of Pediatrics, University of Toronto, Canada M5G 1X8
APStracts 2:0050L, 1995.
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 signalling 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 -receptor (PDGF -R) within 5 min of the onset of strain. Both PDGF-BB and PDGF -R proteins were increased after a 24-h intermittent strain (15 min /h). Phosphorothioate antisense PDGF-B oligonucleotides (ON), at 15 NM, abolished the strain-enhanced DNA synthesis and cell growth. Scrambled PDGF-B ON had no such effect. A neutralizing PDGF-BB antibody (10 Ng/ml) also attenuated strain-induced DNA synthesis. Furthermore, the strain -induced stimulatory effect on DNA synthesis of fetal lung cells was blocked by tyrphostin 9 (1 NM), a PDGF receptor associated tyrosine kinase inhibitor, but not by its inactive structural analogue, tyrphostin 1. Antisense but not sense PDGF -receptor ON (10 NM) 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 -R gene expression. 

Received 7 December 1994; accepted in final form 23 March 1995.
APS Manuscript Number L348-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.