Differential distribution of fibroblast growth factor (FGF)-7 and FGF-10 in L-arginine-induced acute pancreatitis.
The regenerative process of the pancreas after acute pancreatitis (AP) is characterized by acinar and ductal cell proliferation with synthesis and transient deposition of extracellular matrices. Various growth factors were reported to be highly expressed in AP, but their regulation has not yet been clarified. Fibroblast growth factor (FGF)-7, also known as keratinocyte growth factor (KGF), and FGF-10 are members of the FGF family and show high structural homology and similar biological characteristics. Both are mainly synthesized by mesenchymal cells and stimulate epithelial cells via KGF receptor (KGFR) which is a splice variant of FGFR-2. In the present study, we attempted to immunohistochemically determine the localization of FGF-7 and FGF-10 in pancreatic tissues of an L-arginine-induced rat pancreatitis model. Furthermore, highly specific KGFR antibodies were prepared and used for Western blot analysis and immunohistochemistry. In the normal pancreas, FGF-7 was localized in alpha cells of islets, but FGF-10 was not detected. KGFR was also localized in islet cells, ductal cells, and centroacinar cells in the normal pancreas. In the pancreatic tissues of rats with L-arginine-induced pancreatitis, FGF-7 was localized in alpha cells, whereas FGF-10 was expressed in vascular smooth muscle cells (VSMCs). KGFR was not expressed in centroacinar cells and its level decreased after L-arginine treatment. However, KGFR was detected instead in some acinar cells and VSMCs in addition to islet cells. These findings suggest that FGF-7 and FGF-10 contribute to the regeneration and differentiation of acinar cells and angiogenesis in AP through KGFR.
Ishiwata
Toshiyuki
T
Department of Pathology, Nippon Medical School, Tokyo 113-8602, Japan. ishiwata@nms.ac.jp
Naito
Zenya
Z
Lu
Yue Ping
YP
Kawahara
Kiyoko
K
Fujii
Takenori
T
Kawamoto
Yoko
Y
Teduka
Kiyoshi
K
Sugisaki
Yuichi
Y
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001120:Arginine; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D000906:Antibodies; C496465:Fgf10 protein, rat; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D001120:Arginine; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor