title: A novel human fibroblast growth factor treats experimental intestinal inflammation.
abstract: OBJECTIVE
  We recently identified a novel member of the human fibroblast growth factor (FGF) family of signaling molecules, designated FGF-20. In the present study, we examined the activity of this protein in 2 animal models of acute intestinal inflammation and in mechanistic studies in vitro.
  
  
  METHODS
  In vivo experiments consisted of a murine dextran sulfate sodium (DSS) model of colitis and a rat indomethacin model of small intestinal ulceration/inflammation. Cell growth, restitution, gene expression (cyclooxygenase-2 [COX-2] and intestinal trefoil factor [ITF]), and prostaglandin E2 (PGE2) levels were examined in vitro.
  
  
  RESULTS
  In the DSS-colitis model, prophylactic administration of FGF-20 significantly reduced the severity and extent of mucosal damage as indicated by a 55%-93% reduction in luminal blood loss, distal colonic edema, histologic inflammation, and epithelial cell loss relative to animals administered vehicle control. No toxicity was noted during administration of FGF-20 to normal controls. In addition, therapeutic administration of FGF-20 enhanced survival in this model. In the indomethacin-small bowel ulceration/inflammation model, administration of FGF-20 reduced small intestinal weight gain, necrosis, inflammation, and weight loss (36%-53% relative to vehicle control). In vitro studies demonstrated that FGF-20 stimulates growth, restitution, mRNA expression of COX-2 and ITF, and PGE2 levels in human intestinal epithelial cells and enhances the growth of human intestinal fibroblasts.
  
  
  CONCLUSIONS
  FGF-20, having demonstrated therapeutic activity in 2 experimental models of intestinal inflammation, represents a promising new candidate for the treatment of human inflammatory bowel disease.
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D002455:Cell Division / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D003424:Crohn Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D051546:Cyclooxygenase 2; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology*; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D007213:Indomethacin; D007421:Intestine, Small / Q000166:cytology / Q000201:enzymology; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification; D015996:Survival Rate; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; C416003:FGF20 protein, human; C498812:Fgf20 protein, mouse; C498813:Fgf20 protein, rat; D006133:Growth Substances; D007527:Isoenzymes; D008565:Membrane Proteins; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D011994:Recombinant Proteins; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D005346:Fibroblast Growth Factors; D016264:Dextran Sulfate; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin