Expression of keratinocyte growth factor and its receptor in adaptive changes of ileorectal pouch mucosa.
OBJECTIVE
Total proctocolectomy with formation of an ileo-anal pouch is a well-established surgical procedure for patients with ulcerative colitis (UC) or familiar adenomatous polyposis (FAP). The pouch mucosa undergoes adaptive changes, with inflammation of the ileal reservoir being the most common complication. The aetiology is unknown. The keratinocyte growth factor (KGF) has not only been shown to promote intestinal wound healing and re-epithelialization but also to have some immunomodulatory properties. This study was designed to investigate a putative involvement of KGF in observed histomorphological changes in the pouch mucosa.


METHODS
Multiple biopsies were obtained from age-matched and sex-matched patients. Biopsies were stained with H&E and scored for inflammation and morphological changes. mRNA expression levels of KGF and KGF-receptor (KGFR) were determined using competitive RT-PCR, protein expression and phosphorylation was analyzed by Western blotting. KGF and KGFR were localized in tissue samples by immunohistochemistry.


RESULTS
Expression of KGF and KGFR was significantly increased in inflamed and adapting mucosa. Patterns of expression did not significantly differ in pouch mucosa from UC or FAP patients. Protein expression correlated with the mRNA results and KGFR was shown to be activated in adapting pouch mucosa. KGF was detected on subepithelial cells, mainly on fibroblasts, whereas expression of KGFR was restricted to epithelial cells.


CONCLUSIONS
Expression of KGF and KGFR is significantly increased in the pouch mucosa, suggesting an involvement of this growth factor in tissue repair and adaptive changes. Topical application of KGF might alleviate the inflammatory and promote the adaptive process in the ileo-anal pouch mucosa.
Otte
Jan-Michel
JM
Department of Medicine, St. Josef Hospital, Ruhr-University Bochum, Germany.
Boser
Sabine
S
Brunke
Gabriele
G
Kiehne
Karlheinz
K
Schmitz
Frank
F
Banasiewicz
Tomasz
T
Drews
Michail
M
Schmidt
Wolfgang E
WE
Herzig
Karl-Heinz
KH
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D039021:Colonic Pouches / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019449:Pouchitis / Q000378:metabolism / Q000473:pathology; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D018076:DNA, Complementary; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors