Expression of hepatocyte growth factor, keratinocyte growth factor and their receptors in experimental chronic pancreatitis.
BACKGROUND
Hepatocyte (HGF) and Keratinocyte growth factors (KGF) are key factors of tissue organization and regeneration. These peptide growth factors and their receptors c-met and keratinocyte growth factor receptor (KGFR) are overexpressed in pancreatic cancer.


OBJECTIVE
Expression and localization of ligands and receptors were investigated during the development of experimental chronic pancreatitis.


METHODS
Chronic pancreatitis was induced in rats by intravenous injection of dibutyltin dichloride. One to 60 days after treatment, the expression of growth factors and receptors was analysed by competitive polymerase chain reaction, Western blot analysis and immunohistochemistry.


RESULTS
HGF mRNA expression increased (10-fold) until days 7-14 followed by a decrease to control level. Expression of c-met mRNA constantly increased (15-fold). KGF and KGFR mRNA expression were increased after 14-28 days (5-fold) and then returned to control levels. mRNA expression patterns correlated with changes in the protein expression, whereas protein levels of KGF remained unchanged. Ligands were localized in mesenchymal cells and their receptors on epithelial cells.


CONCLUSIONS
The significant increase of HGF and c-met expression suggests an essential role of this growth factor in the morphological changes during the development of chronic pancreatitis. Changes in the expression of KGF and KGFR are less pronounced.
Otte
J M
JM
Department of Internal Medicine, Christian-Albrechts-University, Schittenhelmstrasse 12, 24105 Kiel, Germany.
Schwenger
M
M
Brunke
G
G
Sparmann
G
G
Emmrich
J
J
Schmitz
F
F
Fölsch
U R
UR
Herzig
K H
KH
D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D010195:Pancreatitis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism
C496455:Fgf7 protein, rat; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor