title: Molecular mechanisms of basic fibroblast growth factor effect on healing of ulcerative colitis in rats.
abstract: We demonstrated previously that basic fibroblast growth factor (bFGF) accelerated the healing of experimental duodenal ulcers, and we now hypothesize that bFGF might also accelerate the healing of experimental ulcerative colitis (UC). We also explored the potential molecular mechanisms involved in the accelerated healing of UC in rats treated with bFGF. The results demonstrated that colonic lesions were significantly reduced by bFGF treatment, whereas neutralization of bFGF aggravated iodoacetamide-induced UC. Protein expression of bFGF was increased during the healing stage of UC. Tumor necrosis factor-α levels and myeloperoxidase activity were significantly decreased in UC rats treated with bFGF, whereas they increased in rats treated with anti-bFGF antibody. Real-time polymerase chain reaction and immunohistochemistry showed decreased levels of p27 in the UC rats compared with the healthy controls, which was reversed by bFGF treatment in a dose-dependent manner. By immunohistochemistry and double labeling of Ki-67 and CD34, prominent positive staining of Ki-67 and CD34 was seen after bFGF treatment, indicating the enhanced proliferation of fibroblasts and epithelial and endothelial cells, i.e., angiogenesis. We conclude that bFGF plays a beneficial role in the healing of UC in rats. The molecular mechanisms of bFGF in UC healing not only involve the expected increased cell proliferation, especially angiogenesis, but also encompass the reduction of inflammatory cytokines and infiltration of inflammatory cells. Thus, bFGF enema may be a new therapeutic option for UC.
authors.affiliation: Diagnostic and Molecular Medicine Health Care Group, VA Long Beach Healthcare System, Long Beach, CA 90822, USA.
authors.forename: Brankica
authors.initials: B
authors.lastname: Paunovic
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Deng
authors.forename: Tetyana
authors.initials: T
authors.lastname: Khomenko
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
authors.forename: Ganna
authors.initials: G
authors.lastname: Tolstanova
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tarnawski
authors.forename: Sandor
authors.initials: S
authors.lastname: Szabo
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Sandor
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000166:cytology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D007460:Iodoacetamide; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D043925:Angiogenesis Inducing Agents; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D009195:Peroxidase; D007460:Iodoacetamide