Polyamines are necessary for normal expression of the transforming
growth factor [beta] gene during cell migration.
Wang, Jian-Ying, Mary Jane Viar, Ji Li, Hui-Jun Shi, Shirley A.
McCormack, and Leonard R. Johnson.
Department of Surgery, University of Maryland Medical School and
Baltimore, VA Medical Center, Baltimore, MD 21201, Department of
Physiology and Biophysics, University of Tennessee College of
Medicine, Memphis, TN 38163
APStracts 3:0210G, 1996.
The current study tests the hypothesis that intracellular polyamines
are involved in the regulation of the gene expression of transforming
growth factor beta (TGF[beta]) during epithelial cell migration after
wounding. Administration of [alpha]-difluoromethylornithine (DFMO), a
specific inhibitor of ornithine decarboxylase (ODC, the first rate
-limiting enzyme for polyamine synthesis), depleted cellular
polyamines putrescine, spermidine, and spermine in IEC-6 cells. DFMO
also significantly reduced basal levels of TGF[beta] mRNA in
unwounded cells. The gene expression of TGF[beta] was dramatically
stimulated after wounding a monolayer of the cells not treated with
DFMO. TGF[beta] mRNA levels significantly increased from 4 to 12 h
after wounding, peaking at 6 h at a level 8 times the pre-wounding
control. Increased levels of TGF[beta] mRNA in IEC-6 cells after
wounding were paralleled by increase in TGF[beta] content. Depletion
of intracellular polyamines in the DFMO-treated cells significantly
inhibited the increased expression of the TGF[beta] gene in response
to wounding. Cell migration also significantly decreased in the DFMO
-treated cells. In the presence of DFMO, exogenous TGF[beta] restored
cell migration to normal. These results indicate that 1) polyamine
depletion induced by DFMO is associated with decreases in the
expression of the TGF[beta] gene and cell migration in IEC-6 cells
and 2) exogenous TGF[beta] reverses the inhibitory effect of
polyamine depletion on cell migration. These findings suggest that
polyamines are required for epithelial cell migration in association
with their ability to regulate TGF[beta] gene expression.
Received 6 March 1996; accepted in final form 2 October 1996.
APS Manuscript Number G85-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996