Disease relevance of FGF-2

• Elevated FGF-2 signaling by PASMC and PAEC exposed to increased pulmonary blood flow may play a role in the pulmonary vascular remodeling associated with the shunt model of pulmonary hypertension secondary to congenital heart disease [1].
• We conclude that carotid artery occlusion results in quantifiable white matter lesions that are associated with a loss of MBP from myelin, and that FGF-2, a purported mediator of recovery from brain injury in adult subjects, increases in concentration in proportion to the severity of brain damage in the fetus [2].
• Compared with untreated sheep with aortic stenosis, in heparin-treated sheep LV FGF-2 protein increased 2-fold, whereas FGF-2 mRNA remained unchanged [3].
• CONCLUSIONS: Heparin administration during LV hypertension increases heparin-binding angiogenic factors FGF-2 and VEGF in the LV and ameliorates decreases in LV perfusion capacity and capillary density [3].

High impact information on FGF-2

• Neither growth hormone (GH), fibroblast growth factor-2, nor thyroxine (T(4)) had any effect on IGFBP expression or release [4].
• We have characterized an intracellular binding protein (FGFBP) for FGF-2 that undergoes a juxtanuclear localization coincident with the nuclear translocation of the growth factor [5].
• Fibroblast growth factor-2 (FGF-2) is a potent autocrine mitogen for fetal epiphyseal growth plate chondrocytes and exhibits a transient nuclear translocation during G1 of the cell cycle [5].
• Cells were incubated with protamine sulfate to prevent the binding of endogenous, cell membrane-associated FGF-2 to high affinity FGFRs and their subsequent internalization [5].
• Ligand blot analysis using 125I-labeled FGF-2 showed that a FGFBP of 46-48 kDa (represented by a double band) was present on the nuclear membrane at mid to late G1, and Western blot showed this to be immunologically related to a part of the extracellular domain of the high affinity FGF receptor 1 (FGFR1) [5].

Biological context of FGF-2

• These results demonstrate that mechanical stretch regulates VEGF and FGF-2 gene expression, which could play a role in pulmonary vascular development or in postnatal pulmonary artery function or disease [6].
• We therefore suggest that FGF, and especially FGF-2, play a role in luteal cell proliferation or turnover during early pregnancy, and may thereby contribute to the maintenance of luteal function, which is critical for the successful establishment of pregnancy [7].
• To determine the relationship between cellular proliferation and the presence of FGF-1 and FGF-2 in the ovine corpus luteum (CL) during early pregnancy, ewes received an intravenous injection of bromodeoxyuridine (BrdU) 1 h before slaughter (n = 3/day) on day 12 after estrus (nonpregnant) or on days 12, 18, 24 or 30 after mating (pregnant) [7].

Anatomical context of FGF-2

• FGF-2 protein levels were also increased in the pulmonary arteries and serum of shunt lambs (p < 0.05) [1].
• Perinuclear localization of an intracellular binding protein related to the fibroblast growth factor (FGF) receptor 1 is temporally associated with the nuclear trafficking of FGF-2 in proliferating epiphyseal growth plate chondrocytes [5].
• Basic fibroblast growth factor (FGF-2) was measured in the frontal cortex by ELISA [2].
• Pulmonary artery smooth muscle cells express VEGF and FGF-2 and are subjected to mechanical forces during pulsatile blood flow [6].
• Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells [6].

Associations of FGF-2 with chemical compounds

• In Experiment 2, heparin-, heat-, or trypsin-treatment and immunoneutralization with FGF-1 or FGF-2 antibodies influenced mitogenic activity of all of the peaks [8].

Other interactions of FGF-2

• Maximum expression was found at 24 h and 15% stretch (VEGF: 1.8-fold; FGF-2: 1.9-fold) [6].
• Staining for fibroblast growth factor-2, transforming growth factor-beta, and osteonectin was strongly localized to blood vessels and cells in the vicinity of the annular lesion [9].
• Osteonectin, fibroblast growth factor-2, transforming growth factor-beta, and alpha-smooth muscle cell actin were immunolocalized in sagittal disc sections 3, 6, 12, and 26 months after the operation [9].

Analytical, diagnostic and therapeutic context of FGF-2

• FGFBPs were separated using FGF-2 affinity chromatography [5].
• Expression of VEGF and FGF-2 was determined by Northern blot analysis [6].
• FGF-2 concentrations were higher (p < 0.05) in the I/R-72 than the control group and there was a direct correlation between the pathologic scores (PS) and FGF-2 concentrations (FGF-2 = e((1.6 PS-0.90)) + 743, n = 17, r = 0.73, p < 0.001) [2].
• The five peaks of mitogenic activity were further purified by using chromatography, then were concentrated and subjected to SDS-PAGE and Western analysis for FGF-2 [8].
• Moreover, FGF-2 was immunolocalized by using a primary antibody and fluorescein isothiocyanate (FITC)-labeled secondary antibody, and immunofluorescence was quantified by using an interactive laser cytometer and image analysis [7].

References