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-␣ 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.

Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats

“…The assessment of hematological parameters can be used to determine the extent of disease state of colitis[13]. TNF-α, IL-1β, IL-6 and IL-8 like cytokines were released via the activation of white blood cells (including macrophages) via neutrophils[36]. This may have resulted in diarrhoea and malena.…”

“…The SOD content was determined as previously described by Misra and Fridovich[35] and SOD activity was expressed as U/mg protein. Glutathione (GSH) assay was performed according to the method of Moron et al (1979)[36] and the amount of reduced GSH was expressed as µg of GSH/mg protein. Myeloperoxidase (MPO) content was measured using the method of Krawisz et al (1984)[37] and MPO activity was defined as the quantity of enzyme degrading 1 µmol of peroxide per minute at 25°C and was expressed in units per gram (U/g) of wet scrapings.…”

Angiogenesis in Inflammatory Bowel Disease

“…It was shown that increased syndecan-1, TNF- α , and bFGF levels of patients with active IBD were declined after infliximab therapy [ 52 ]. In contrast, Paunovic et al [ 53 ] demonstrated that bFGF caused mucosal healing of ulcerative colitis in rat. Hepatocyte growth factor (HGF) is secreted from stromal cells present within the inflammatory tissue and activated by hepatocyte growth factor activator (HGFA).…”

“…For fibrosis, targeting collagen cross-linking enzymes (LOX family) is a new interesting issue [ 61 ]. Other natural antiangiogenic molecules studied for the therapy of IBD are Ang1 [ 40 ], TGF- β [ 50 ], bFGF [ 53 ], HGF [ 57 ], Cav-1 [ 72 ], and endoglin [ 11 ]. But use of these molecules needs more time and study.…”

The effect of stromal vascular fraction and Platelet-Rich Plasma combination on basic Fibroblast Growth Factor serum level during anal trauma healing in a Wistar rat model

“…An intestinal fistulation study by Gao et al also found similar results [ 40 ]. Another study on ulcerative colitis induced with iodoacetamide found decreased bFGF levels in the first 6 h, which then increased until the 10th day of the study [ 41 ]. However, these results differ from those of a study on rat burn injury by Mansoub et al who found an increase in bFGF until the 7th day, followed by a decrease on the 14th day [ 30 ].…”