Disease relevance of FGF18

• FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate [1].
• Our results indicate that FGF18 is activated in colon cancers as a direct downstream target of the Wnt signaling pathway and that it might represent a marker for early diagnosis and a molecular target for treatment of this life-threatening tumor [2].
• FGF18 mRNA was expressed in fetal lung, fetal heart, lung carcinoid, colorectal cancer, and ovarian cancer [3].
• Two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of FGF-5 and FGF-18 [4].

Psychiatry related information on FGF18

• Significant reductions in infarct volumes and reductions in deficits of reference memory and motor activity were also observed with FGF18 infused 24 hours after MCAO [5].
• Infusion of FGF18 reduced infarct volumes and improved scores in tests of reference and working memory, motor ability, and exploratory behavior [5].
• As a first step towards elucidating the roles of these FGF in human development, we examined FGF18 and FGF23 mRNA expression by in situ hybridization in whole human embryos at 30 days and 8 weeks of gestation (GW) and in specific fetal tissues at different ages [6].

High impact information on FGF18

• This result is consistent with Fgf17 and Fgf18 being expressed in the midbrain and not just in r1 as Fgf8 is [7].
• Direct Interactions of Runx2 and Canonical Wnt Signaling Induce FGF18 [8].
• Here we show that an essential regulator of bone development, FGF18, is a direct target of canonical Wnt signaling [8].
• A single DNA binding site for the Wnt-dependent transcription factors TCF/Lef accounted for the stimulation of the fgf18 promoter in response to Wnt signaling [8].
• Based on these and other experiments it has been proposed that FGF18 signals through FGFR3 to promote cartilage production by chondrocytes [9].

Biological context of FGF18

• These findings support a model in which FGF18 regulates skeletal vascularization and subsequent recruitment of osteoblasts/osteoclasts through regulation of early stages of chondrogenesis and VEGF expression [1].
• HUVEC clearly demonstrated chemotaxis towards FGF16 and FGF18 [10].
• We showed that exogenous FGF18 promoted growth of NIH3T3 cells in an autocrine manner and that transfection of FGF18 short interfering RNAs suppressed growth of colon cancer cells in culture [2].
• Administration of vehicle or FGF18 had no significant effect on mean arterial blood pressure, heart rate, brain temperature, blood pH, Pco2, or Po2 [5].
• Assignment of fibroblast growth factor 18 (FGF18) to human chromosome 5q34 by use of radiation hybrid mapping and fluorescence in situ hybridization [11].

Anatomical context of FGF18

• We further show that FGF18 is necessary for Vegf expression in hypertrophic chondrocytes and the perichondrium and is sufficient to induce Vegf expression in skeletal explants [1].
• However, this delay in mineralization could not be simply explained by FGF18 signaling to osteoblasts [1].
• Fgf18 expression was earlier reported in the liver, and we detected FGF18 expression in liver vascular and liver sinusoidal endothelial cells (LSECs), but not in hepatic parenchymal cells [10].
• In the VSMC of rat aortic tissue and in HUASM cultured cells we could demonstrate FGF18 immunoreactivity in the nucleus of the cells [12].
• Recombinant FGF18 stimulated DNA synthesis in primary hepatocytes, suggesting, that endothelial FGF18 might have a paracrine function in promoting growth of the parenchymal tissue [10].

Associations of FGF18 with chemical compounds

• In addition, vitamin A, which is known to enhance alveolar development, elevated FGF-18 and elastin expressions in day 2 lungs, thus advancing the biological increase [13].

Other interactions of FGF18

• In the present report, we confirmed by RT-PCR analysis that FGF18 is wildly expressed in the cardiovascular tissue, while FGF16 showed a more restricted expression pattern [10].
• FGF18, FGF20 and SPRY4 are potent targets of the canonical WNT signaling pathway in the gastrointestinal tract [14].
• Sequence comparison indicates that FGF-18 is conserved with the other FGFs and most homologous to FGF-8 among the FGF family members [15].
• Studies mostly performed in rodents and chicken have demonstrated that FGF18 is a pleiotropic growth factor involved in the development of various organs, while there are no data supporting a direct role of FGF23 in cell proliferation or differentiation either in physiology or pathology in any species [6].

Analytical, diagnostic and therapeutic context of FGF18

• In situ hybridization revealed that FGF18 mRNA is mainly expressed in the anagen inner root sheath and telogen bulge of hair follicles [16].
• The expression of FGF-18 mRNA was examined in adult rat tissues and embryos by Northern blotting analysis and in situ hybridization [17].
• Significant rescue from photoreceptor cell death was found after injections of vectors expressing either FGF-5 or FGF-18 in the animal models [4].
• To assess the time window for fibroblast growth factor-18 (FGF18)-mediated neuroprotection, FGF18 was administered by intravenous infusion at various times after transient occlusion of the middle cerebral artery (MCAO) in rats [5].

References