Effects of keratinocyte growth factor (KGF) on gut growth and repair.
Keratinocyte growth factor (KGF) is a mitogen found throughout the gastrointestinal 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. Changes in gut growth (wet weight and vincristine-induced metaphase arrest) were then assessed. The effects of KGF on gastric repair and acid secretion in rats were 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-induced accumulation of metaphases in the stomach and small intestine but not in the colon. Plasma gastrin, peptide YY, enteroglucagon, and glucagon-like peptide-1 were all increased, whereas insulin was lowered by KGF (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). These studies support the idea that KGF is involved in the control of proliferation of the gastrointestinal tract. They do not provide evidence, however, for a role in the early reparative process invoked during short-term models of gastrointestinal injury.
Playford
R J
RJ
Department of Medicine and Therapeutics, University of Leicester, U.K.
Marchbank
T
T
Mandir
N
N
Higham
A
A
Meeran
K
K
Ghatei
M A
MA
Bloom
S R
SR
Goodlad
R A
RA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002455:Cell Division / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects* / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005744:Gastric Acid / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology* / Q000627:therapeutic use; D006728:Hormones / Q000097:blood; D007213:Indomethacin; D008297:Male; D010289:Parenteral Nutrition, Total; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D006728:Hormones; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D007213:Indomethacin