Diabetes, Vol 42, Issue 5 746-756, Copyright © 1993 by American Diabetes Association
Synthesis and expression of transforming growth factor beta-1, beta-2, and beta-3 in the endocrine and exocrine pancreas
Y Yamanaka, H Friess, M Buchler, HG Beger, LI Gold and M Korc
Department of Medicine, University of California, Irvine 92717.
The actions of transforming growth factor-beta isoforms as potent
regulators of growth and differentiation have led to the examination of
their presence in the human pancreas. The cellular localization of TGF-beta
1, TGF-beta 2, and TGF-beta 3 was assessed in the normal human pancreas by
using immunohistochemical and in situ hybridization techniques. Although
cytoplasmic immunoreactivity for TGF-beta 1, TGF-beta 2, and TGF-beta 3 was
found in islet cells, acinar cells, and ductal cells, a differential
immunostaining pattern for TGF-beta isoforms was observed. In the endocrine
pancreas, the islet cells demonstrated diffuse cytoplasmic immunostaining
for TGF-beta 1, TGF-beta 2, and TGF-beta 3. However, only TGF-beta 2 and
TGF-beta 3 exhibited an intense pattern of immunostaining in a few
endocrine cells. Most of the positive islet cells coexpressed insulin. In
contrast, in the exocrine pancreas, a greater number of acinar cells showed
immunoreactivity for TGF-beta 1 than for TGF-beta 2 and TGF-beta 3. In the
ductal cells, all three TGF-beta isoforms showed a similar intensity and
pattern of immunostaining and were observed more frequently in the smaller
distal ductules than in the larger pancreatic ducts. TGF-beta 1 and
TGF-beta 3, but not TGF-beta 2, immunostaining was detected strongly in the
smooth muscle cells and weakly in the endothelial cells of the blood
vessels, whereas the fibroblasts of the interstitium were completely
negative. In situ hybridization revealed that mRNA encoding all three
TGF-beta isoforms colocalized with their respective proteins in islets,
acinar cells, and ductal cells. In contrast, mRNA expression was absent in
the smooth muscle cells and endothelium of the vessels. These results
suggest that TGF-beta isoforms may act by both autocrine and paracrine
mechanisms in the pancreas. The differential pattern of expression observed
for each TGF-beta isoform implies unique roles for these proteins in the
regulation of the endocrine and exocrine pancreas.