Regulated stimulation of epithelial cell dna synthesis by fibroblast-derived mediators. Pasternack, Morris, Xiaoli Liu, Robert A. Goodman, and D. Eugene Rannels. Departments of Medicine, Cellular & Molecular Physiology, and Anesthesia
APStracts 3:0226L, 1996.
Interactions of interstitial fibroblasts with nearby epithelial cells are thought to play a role in lung growth and development. The present studies support this premise. Medium conditioned by second passage lung fibroblasts (FCM) stimulated both DNA synthesis and accumulation in low density (2x104/cm2) cultures of type II alveolar epithelial cells. FCM effects did not require serum; they were time- and dose-dependent, with half-maximal FCM activity at 1:8 dilution. A maximal response to FCM required 30 hours' exposure. FCM activity was reduced in medium from fibroblasts treated with dexamethasone, suggesting physiological regulation. Type II cells subjected to cyclic mechanical stress demonstrated an increased response to FCM, as compared to static cultures. FCM activity did not appear to be accounted for by hepatocyte growth factor, by keratinocyte growth factor, by acidic fibroblast growth factor, nor by fibronectin. These results suggest that early-passage lung fibroblasts release, by regulated pathways, one or more factors that stimulate DNA synthesis by type II cells. Sensitivity to FCM appears to be elevated in type II cell cultures subjected to cyclic mechanical stress. 

Received 14 June 1996; accepted in final form 1 November 1996.
APS Manuscript Number L181-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996