Epidermal growth factor secreted from the salivary gland is
necessary for liver regeneration.
Jones, David E., Jr, Rose Tran-Patterson, Dong-Ming Cui, Dennis Davin,
Kimberly P. Estell, and Donald M. Miller.
From the Departments of Internal Medicine, the Department of
Biochemistry and Molecular Genetics, and the Bolden Laboratory, The
University of Alabama at Birmingham, and the Birmingham Veterans
Affairs Medical Center, Birmingham, Alabama
APStracts 2:0012G, 1995.
Partial hepatectomy (PH) in rats induces a synchronized burst of DNA
replication in the remnant liver which peaks at 24 hours post
-hepatectomy. We report here that removal of the major salivary glands
prior to one-third and two-thirds PH prevents the proliferative
response in the remaining liver. Twelve days after 1/3 PH, the
remnant liver is 89% of the normal liver weight in non-salivectomized
rats, but only 55% in salivectomized animals. This indicates that
salivectomy does not merely delay the first round of cell division
but that it prevents actual regeneration. Salivectomy alters the
early protooncogene response to partial hepatectomy. In
salivectomized rats, the characteristic peak of c-myc mRNA synthesis
at 2-4 hours following PH is significantly decreased as compared to
non-salivectomized rats. The peak of DNA synthesis at 24 hours
following partial hepatectomy in salivectomized rats is also
dramatically decreased. DNA synthesis as measured by [3H]
-thymidine incorporation into DNA of hepatic cells is decreased
approximately 90% in salivectomized rats versus non-salivectomized
rats 22-26 hours following PH. Ligation of the venous drainage of the
salivary gland results in the same inhibitory effect on DNA synthesis
indicating that the salivary gland must release (a) circulating
factor(s) and indicates that the early increase in c-myc expression
and the subsequent DNA synthesis, both of which reflect the
stimulation of cellular proliferation in the regenerating liver, are
induced by humoral factor(s) released from the salivary glands.
Injection of exogenous EGF in salivectomized rats results in
restoration of both the DNA synthetic and c-myc responses at levels
characteristic of those of liver regeneration. Thus, our results
suggest that salivary gland release of EGF may trigger the early
events of liver regeneration.
Received 22 August 1994; accepted in final form 10 January 1995
APS Manuscript Number G314-3.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.