Human keratinocyte growth factor-2 (KGF-2) is a member of the
fibroblast growth factor family that promotes healing of experimental small intestinal ulceration and
colitis. The aim of this study was to determine whether
repifermin, a truncated form of recombinant human KGF-2, reverses abnormalities in colonic mucosal transport in a murine model of
dextran sulfate sodium (DSS)-induced
colitis. Male Swiss-Webster mice were given 4% DSS in
drinking water for 7 days and then normal
drinking water for 3 days.
Repifermin (5 mg kg(-1), i.p.) or vehicle was administered daily for 7 days starting on Day 4 of DSS exposure. On Day 10, net ion transport was measured electrophysiologically in colonic mucosal sheets.
Repifermin significantly reduced DSS-induced colonic
inflammation measured by tissue
myeloperoxidase activity. Concurrently, in colonic tissue taken from mice treated with
repifermin, there was a normalization of basal potential difference and short circuit current, and an improvement in the secretory responses to stimulation of
muscarinic and ganglionic
cholinoceptors. In control mice,
repifermin did not interact directly with colonic epithelial cells or intramural neurones to induce immediate changes in net electrogenic transport. The results suggest that
repifermin therapy may improve the mucosal electrogenic transport that is impaired during
colitis.