Efficacy of repifermin (keratinocyte growth factor-2) against abnormalities in gastrointestinal mucosal transport in a murine model of colitis.
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.
Greenwood-Van Meerveld
B
B
Oklahoma Foundation for Digestive Research, Basic Science Laboratories, Veterans Administration Medical Center, Room 151, 921 NE 13th Street, Oklahoma City, OK 73104, USA. Beverley-Greenwood@ouhsc.edu
Venkova
K
K
Connolly
K
K
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D003092:Colitis / Q000188:drug therapy* / Q000662:veterinary; D003106:Colon / Q000502:physiology*; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D004594:Electrophysiology; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D007249:Inflammation; D007413:Intestinal Mucosa / Q000502:physiology*; D017136:Ion Transport / Q000187:drug effects*; D008297:Male; D051379:Mice; D009195:Peroxidase / Q000494:pharmacology
D000925:Anticoagulants; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors; D016264:Dextran Sulfate; D009195:Peroxidase