Vol. 276, Issue 1, G193-G198, January 1999
Fibroblasts stimulate acinar cell proliferation through IGF-I
during regeneration from acute pancreatitis
C. U.
Ludwig,
A.
Menke,
G.
Adler, and
M. P.
Lutz
Department of Internal Medicine I, University of Ulm, D-89070 Ulm,
Germany
Pancreatic regeneration after caerulein-induced
pancreatitis is characterized by transient fibroblast proliferation
followed by replication of acinar cells. The mechanisms that coordinate regeneration are incompletely understood. In this study, we examine the
role of insulin-like growth factor I (IGF-I). Acute edematous pancreatitis was induced in rats by 12 h caerulein infusion. Pancreatic IGF-I mRNA levels increased over 50-fold during regeneration, reaching
a maximum at day 2. Immunohistochemically, IGF-I was localized to fibroblasts within the areas of interstitial tissue. IGF-I
mRNA was demonstrated in primary cultures of pancreatic fibroblasts but
not in cultured pancreatic acinar cells. However, with the use of
Western blotting acinar cells did express IGF-I receptors. IGF-I
stimulated 5-bromo-2'-deoxyuridine uptake and increased numbers
of acinar cells in a dose-dependent manner. Stimulation was half
maximal at 1.1 nM and completely inhibited by an IGF-I antagonist and
by IGF binding protein-3 (IGFBP-3). Possible paracrine regulation was
confirmed by stimulation of acinar cell proliferation with
fibroblast-conditioned medium, which was partially inhibited by IGF-I
antagonist or by IGFBP-3. We conclude that acinar cell proliferation
during late regeneration from pancreatitis is mediated at least in part
by paracrine release of IGF-I from fibroblasts.
pancreas; insulin-like growth factor I; insulin-like growth factor
binding protein-3; injury
