Expression of keratinocyte growth factor and its receptor in adaptive changes of ileorectal pouch mucosa.

Abstract

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.

MATERIALS AND 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.

CONCLUSION:

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.

• Authors: Jan-Michel Otte, Sabine Boser, Gabriele Brunke, Karlheinz Kiehne, Frank Schmitz, Tomasz Banasiewicz, Michail Drews, Wolfgang E Schmidt, Karl-Heinz Herzig
• Journal: Scandinavian journal of gastroenterology (Scand J Gastroenterol) Vol. 40 Issue 9 Pg. 1066-75 (Sep 2005) ISSN: 0036-5521 [Print] England
• PMID: 16211713 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• DNA, Complementary
• Receptors, Fibroblast Growth Factor
• Fibroblast Growth Factors

Topics

• Adolescent
• Adult
• Aged
• Biomarkers (metabolism)
• Biopsy
• Blotting, Western
• Colonic Pouches (physiology)
• DNA, Complementary (genetics)
• Endoscopy, Gastrointestinal
• Female
• Fibroblast Growth Factors (biosynthesis, genetics)
• Humans
• Immunohistochemistry
• Intestinal Mucosa (metabolism, pathology)
• Male
• Middle Aged
• Pouchitis (metabolism, pathology)
• Receptors, Fibroblast Growth Factor (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction