AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 230-L238, Copyright © 1995 by American Physiological Society
Insulin modulation of bronchial epithelial cell fibronectin in vitro
D. J. Romberger, P. Pladsen, L. Claassen, M. Yoshida, J. D. Beckmann and S. I. Rennard
Research Service, Department of Veterans Affairs Medical Center, Omaha, Nebraska 68105.
Fibronectin (Fn) is involved in the migration of epithelial cells in
re-epithelialization of wounds. Epithelial cell-derived Fn is particularly
potent as a chemotactic factor for bronchial epithelial cells (BECs) in
vitro. Thus modulation of airway epithelial cell Fn may be a key aspect of
airway repair. Insulin is both an important growth factor and known
chemotactic factor for cultured BECs. We postulated that insulin may
modulate Fn production of cultured BECs. We examined this hypothesis
utilizing bovine BECs in culture with serum-free media with and without
insulin. BECs grown in media without insulin released more Fn into culture
supernatants and contained more Fn in cell layers than cells grown with
insulin. Labeling of cells with [35S]methionine demonstrated an increase in
new protein production and Fn mRNA expression was increased. Increased Fn
in BEC cultures without insulin was associated with an increase in active
transforming growth factor-beta (TGF-beta) release as measured by a
standard bioassay. Increased BEC Fn in cultures without insulin was
partially inhibited by exposure of cultures to TGF-beta antibody. Thus
insulin appears to modulate BEC Fn production in vitro in part through a
TGF-beta-dependent mechanism. Insulin may be involved in airway repair
mechanisms through modulation of epithelial cell Fn production.
