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.
Footnotes
This study was supported by Department of Veterans Affairs, Veterans Health Administration Merit Review Grants [VAMR0710-580, VAMR0810-877] (to Z.S. and S.S.).
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.111.183665.
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ABBREVIATIONS:
- UC
- ulcerative colitis
- IBD
- inflammatory bowel disease
- IA
- iodoacetamide
- bFGF
- basic fibroblast growth factor
- MPO
- myeloperoxidase
- TNF-α
- tumor necrosis factor-α
- VEGF
- vascular endothelial growth factor
- PCR
- polymerase chain reaction
- GAPDH
- glyceraldehyde-3-phosphate dehydrogenase
- BrdU
- bromodeoxyuridine
- rMVEC
- rat microvascular endothelial cell
- PBS
- phosphate-buffered saline
- DSS
- dextran sulfate sodium
- TGF-β
- transforming growth factor-β.
- Received May 6, 2011.
- Accepted August 11, 2011.
- U.S. Government work not protected by U.S. copyright
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