Disease relevance of FGF9

• Exogenous administration of TGFbeta1 to cultures of hereditary multiple exostosis eliminates FGF9 expression [1].
• Role of FGF9 and FGF receptor 3 in osteochondroma formation [1].
• Elevated levels of FGF 9, its specific ligand, have been found in synovial fluids of patients with synovial chondromatosis [2].
• The expression of FGF-9 was greater in the early stage of endometriosis, compared with the severe stage, which is consistent with concentration of 17 beta-estradiol in the peritoneal fluid of women with endometriosis [3].
• FGF-9 potentially regulates proliferation and GFAP expression in human gliomas either in the presence or in the absence of the endogenous growth factor expression [4].

Psychiatry related information on FGF9

• METHODS: GAF, BPRS, DAS (at baseline and after 6 months), LQL and VSSS (at follow-up only) were administered to 194 patients attending the South-Verona community-based mental health service [5].
• Psychopathology was measured using BPRS, and social functioning using GAF [6].
• Only 5.1% of male patients with psychoactive substance use disorder and disciplinary problems in school had a non-negative outcome, while as many as 76.6% of female patients without psychoactive substance use and a DSM-IV GAF of > or = 40 at hospitalization had a non-negative outcome at 15 years follow-up [7].
• Recommendation of psychotherapy was predicted by the absence of a personality disorder and high GAF scores, but not by the presence of a psychiatric syndrome [8].
• BN+AD+ women were more likely than BN+AD- women to have drug dependence, conduct disorder, and suicidality, and were more likely to have major depression, lower GAF scores, and to engage in unsafe sex than both BN+AD- and BN-AD+ women [9].

High impact information on FGF9

• Interferon-gamma (IFN-gamma) induces the transcription of the gene encoding a guanylate binding protein by activating a latent cytoplasmic factor, GAF (gamma-activated factor) [10].
• The time course of activation of GAF was different in fibroblasts and HeLa cells and correlated well with IFN-gamma-induced transcriptional activation in both cell types [11].
• Crystal structure of the tandem GAF domains from a cyanobacterial adenylyl cyclase: modes of ligand binding and dimerization [12].
• Constructs containing an Asp/Ala mutation in either GAF domain still showed positive cooperative cAMP stimulation but with reduced Hill coefficients [13].
• We report here that prostaglandin E(2) (PGE(2)) induces expression of FGF-9, which promotes endometriotic stromal cell proliferation, through the EP3 receptor-activated protein kinase Cdelta (PKCdelta) signaling pathway [14].

Chemical compound and disease context of FGF9

• 5. Preincubation with TLCK, PDTC or infection with IkappaBalpha adenovirus abolished LPS-stimulated GAS/GAF DNA-binding [15].
• This is achieved through interactions with 2-oxoglutarate, a key metabolic signal of the carbon status, which binds to the N-terminal GAF (cGMP-specific and stimulated phosphodiesterases, Anabaena adenylate cyclases and Escherichia coli FhlA) domain of NifA [16].
• Since GAF was considered to be one of the stimuli for inflammation in acne vulgaris, administration of tetracycline and 13-cis-retinoic acid appears to be an adequate therapy [17].
• Tetracycline and 13-cis-retinoic acid inhibit production and activity of granulocyte activating factor (GAF) from Propionibacterium acnes [17].

Biological context of FGF9

• Downregulation of FGF9 may provide a possible nonoperative therapy for PSC [2].
• To elucidate the molecular mechanism of FGF9 dimerization, the crystal structure of FGF9 was determined at 2.2 A resolution [18].
• A significant surface area (>2000 A(2)) is buried in the dimer interface that occludes a major receptor binding site of FGF9 [18].
• The capability of proliferation possessed by endometriotic stromal cell during menstruation when ovarian 17 beta-estradiol is in the nadir may be mediated, at least in part, by autocrined estrogen-stimulated expression of FGF-9 and its receptors [3].
• Whereas a dramatic effect on cell numbers was observed after the addition of 1-10 micrograms FGF-9/ml, a lesser effect could be achieved by FGF-8 or KGF [19].

Anatomical context of FGF9

• FGF9 is an autocrine and paracrine prostatic growth factor expressed by prostatic stromal cells [20].
• FGF9 is an abundant secreted growth factor that can act as both a paracrine mitogen for epithelial cells and an autocrine mitogen for stromal cells [20].
• We demonstrated that FGF9 is expressed in a subpopulation of the RPE, as well as photoreceptors and other neurons of the retina [21].
• Synoviocytes but not chondrocytes from affected patients express FGF9 in culture [2].
• Expression at the mRNA level of FGF9, FGFR3, and collagen type IIa is found in these cells, but not in skin fibroblasts from afflicted or healthy individuals [1].

Associations of FGF9 with chemical compounds

• Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor- and heparin-binding interfaces [22].
• Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen [3].
• Fibroblast growth factor-9 (FGF-9) is a steroid-regulated mitogen and survival factor for nerve and mesenchymal cells [3].
• Concordant with this result, treatment of endometriotic stromal cells with 4-hydroxyandrostenedione (an aromatase inhibitor) or ICI 182,870 inhibited their proliferation, and that was reversed by coadministration with 17 beta-estradiol or FGF-9 [3].
• Expression of FGF-9 in stromal cells was induced by 17beta-estradiol but not by progesterone [23].

Regulatory relationships of FGF9

• Interestingly, binding of both mutant receptors to FGF9 was notably enhanced and implicates FGF9 as a potential pathophysiological ligand for mutant FGFRs in mediating craniosynostosis [24].
• Evidence that beta-catenin and TCFs regulate FGF9 expression in several epithelial cell lines was obtained [25].
• These studies provide evidence to demonstrate, for the first time, that a novel signaling cascade involving phospholipase Cgamma, calcium, mTOR, and S6K1 is activated by FGF9 in a receptor-specific manner [26].

Other interactions of FGF9

• Analysis of FGF8 and FGF9 binding to chimeric receptors showed that a broad region spanning Ig domain II and sequences further N-terminal determines binding specificity for these ligands [27].
• Since receptor activation can result in its movement to a perinuclear localization, an alternative explanation for the redistribution of FGFR-3-IIIb could be different degrees of activation by a ligand (FGF1 or FGF9) [28].
• Synovial chondromatosis: the possible role of FGF 9 and FGF receptor 3 in its pathology [2].
• The results from previous studies for these receptors imply that FGF9 or FGF4 could act as ligands [21].
• In contrast to FGF2, which blocked chondrocytic differentiation, FGF9 had no effect on differentiation but inhibited terminal differentiation [29].

Analytical, diagnostic and therapeutic context of FGF9

• No FGF9 was detected by immunohistochemistry in breast tissues [28].
• Western blot analysis of tissue extracts from the normal and hyperplastic transition zone shows that FGF9 is present at two to threefold higher levels in the hyperplastic transition zone [20].
• Expression patterns of FGFR3 and its specific ligand, fibroblast growth factor 9 (FGF 9), were evaluated both in situ and in cell cultures [2].
• Using quantitative RT-PCR analysis, we found that FGF-9 mRNA was expressed primarily by endometrial stromal cells [23].
• In conclusion, the results demonstrate for the first time that human blood and bronchoalveolar lavage gammadelta T-lymphocytes are capable of expressing FGF-9 [30].

References