EFFECTS OF KERATINOCYTE GROWTH-FACTOR (KGF) ON GUT GROWTH AND REPAIR

Keratinocyte growth factor (KGF) is a mitogen found throughout the gas trointestinal tract, but its role in gastrointestinal pathophysiology is unclear. The effect of recombinant KGF on gut growth and repair has been examined using a variety of in vivo models. Rats receiving total parenteral nutrition had co-infusions of KGF or control for 6 days. C hanges in gut growth (wet weight and vincristine-induced metaphase arr est) were then assessed. The effects of KGF on gastric repair and acid secretion in rats tr ere determined using an indomethacin (20 mg/kg)/ restraint model and animals fitted with chronic gastric fistulae. KGF at 0.1, 1, and 3 mg/kg increased gut growth as assessed by wet weight throughout the gastrointestinal tract and increased vincristine-induce d accumulation of metaphases in the stomach and small intestine but no t in the colon. Plasma gastrin, peptide YY, enteroglucagon, and glucag on-like peptide-1 were all increased, whereas insulin was lowered by K GF (all P<0.01). KGF was ineffective in reducing indomethacin-induced gastric damage but caused a reduction in basal acid secretion of about 35 and 50 per cent when administered at 0.2 or 5 mg/kg (P<0.05). Thes e studies support the idea that KGF is involved in the control of prol iferation of the gastrointestinal tract. They do not provide evidence, however, for a role in the early reparative process invoked during sh ort-term models of gastrointestinal injury. (C) 1998 John Wiley & Sons , Ltd.