Fibroblasts stimulate acinar cell proliferation through IGF-I during regeneration from acute pancreatitis.
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.
Ludwig
C U
CU
Department of Internal Medicine I, University of Ulm, D-89070 Ulm, Germany.
Menke
A
A
Adler
G
G
Lutz
M P
MP
D000208:Acute Disease; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004487:Edema / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005347:Fibroblasts / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017451:Receptors, Somatomedin / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D014018:Tissue Distribution
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I