Alleviation of experimental ulcerative colitis with the synthetic peptide, F2A4-K-NS (fibratide)

• Published in: Digestive diseases and sciences Vol. 52; no. 9; pp. 2054 - 2062
• Main Authors: XINHUA LIN, ZAMORA, Paul O, TAKAHASHI, Kazu, YI LUI
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.09.2007; Springer Nature B.V
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Cell Proliferation - drug effects; Cells, Cultured; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - pathology; Dextran Sulfate - toxicity; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Fibroblast Growth Factor 2 - administration & dosage; Fibroblast Growth Factor 2 - chemical synthesis; Gastroenterology. Liver. Pancreas. Abdomen; Injections, Intraperitoneal; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Other diseases. Semiology; Plasma Substitutes - toxicity; Recombinant Proteins - chemical synthesis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Outcome; Ulcerative colitis .Growth factor; Peptides; Oral administration; Oral delivery; Digestive diseases; Intestinal disease; Mimetic peptide; Inflammatory disease; Ulcerative colitis; Epithelial
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-006-9641-z

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.