Alleviation of experimental ulcerative colitis with the synthetic peptide, F2A4-K-NS (Fibratide).
Recombinant fibroblast growth factors (FGFs) maintain the integrity of the gut epithelium and reduce mucosal injury in experimental inflammatory bowel disease (IBD). Chemically synthesized FGF mimetics could potentially extend the utility of FGFs by tailoring them for optimal bioactivity and oral administration, for example. Here, F2A4-K-NS (Fibratide), a synthetic FGF mimetic peptide, alleviated dextran sulfate sodium (DSS)-induced ulcerative colitis in mice when delivered systemically and, to a lesser extent, orally. Intraperitoneal injection of Fibratide (1 or 5 mg/kg/day) ameliorated DSS-induced ulcerative colitis, resulting in reduced weight loss, decreased colon wall thickening, and increased colon length. Fibratide also improved epithelial integrity by reducing histological-detectable crypt damage and inflammation. Orally administered Fibratide (1 mg/kg/day) was also effective in ameliorating symptoms with effects generally similar to those of intraperitoneal injection. In vitro studies were conducted to help clarify how Fibratide might act in vivo. Fibratide exhibited a modest enhancement of epithelial cell proliferation. On the other hand, Fibratide doubled the rate of epithelial cells migration and restitution in a cell culture model of wound repair. Collectively, the results indicate that Fibratide reduced the severity of experimental ulcerative colitis and may be potentially useful in the treatment of IBD.
Lin
Xinhua
X
BioSurface Engineering Technologies, Inc., 9430 Key West Avenue, Suite 220, Rockville, Maryland 20850, USA. xlin@biosetinc.com
Zamora
Paul O
PO
Takahashi
Kazu
K
Lui
Yi
Y
D000284:Administration, Oral; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000138:chemical synthesis; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010952:Plasma Substitutes / Q000633:toxicity; D011994:Recombinant Proteins / Q000138:chemical synthesis; D016896:Treatment Outcome
D010952:Plasma Substitutes; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016264:Dextran Sulfate