Disease relevance of FST

• Presence of activin, inhibin, and follistatin in epithelial ovarian carcinoma [1].
• In addition, the effects of follistatin and activin A on DNA synthesis of normal as well as preneoplastic hepatocytes and hepatoma cells were analysed [2].
• The objective of this study was to quantify the relative expression of inhibin alpha, inhibin/activin beta(A), beta(B), beta(C), follistatin, activin receptors and beta-glycan genes in placental tissue of term pre-eclamptic patients and controls to investigate if these genes are up-regulated in the placenta in pre-eclampsia [3].
• Inhibin subunits, follistatin and activin receptors in the human teratocarcinoma cell line Tera-2 [4].
• Follistatin-related gene expression, but not follistatin expression, is decreased in human endometrial adenocarcinoma [5].
• This is the first report to show the role of FST in metastases [6].

Psychiatry related information on FST

• AIMS: To define clinically relevant cut-off points for severe fear of self-injecting (FSI) and self-testing (FST) (phobia) in insulin-treated patients with diabetes, and to estimate the magnitude of these phobias in our research population [7].
• Individuals with high dental fear had a statistically significantly higher number of decayed surfaces (DS), decayed teeth, (DT) and missing teeth (MT) but a statistically significantly lower number of filled surfaces (FS), filled teeth (FT), functional surfaces (FSS), and functional teeth (FST) [8].
• Exogenous administration of FS and related muramyl peptides results in an increase in slow-wave sleep (SWS) [9].

High impact information on FST

• In the process other factors such as activin and follistatin were serendipitously discovered [10].
• Ruiz i Altaba describes a possible model for anteroposterior patterning involving ;lanar signals for amphibian, avian and mammalian embryos, compares the axial patterning of the neural plate with the patterning of insect epithelia, and discussed possible roles of noggin, follistatin and hedgehog-related genes in neural induction and patterning [11].
• Follistatin was first described in 1987 as a follicle-stimulating hormone inhibiting substance present in ovarian follicular fluid [12].
• In this review we focus on the biochemical characteristics of follistatin and its interaction with activin and discuss the emerging role of these proteins as potent tissue regulators in the gonad, pituitary gland, pregnancy membranes, vasculature, and liver [12].
• Areas identified as motion sensitive included V2, V3, MT/V5, vMST, FST, VIP, and FEF (with moving dots), as well as V4, TE, LIP, and PIP (with random lines) [13].

Chemical compound and disease context of FST

• Using a proteomic approach to screen for new growth factors released by melanoma cells, we identified follistatin as a major heparin-binding factor in medium conditioned by the Bowes melanoma cell line [14].
• Reduced activin biosynthesis, increased follistatin secretion, or signaling defects in the activin receptor system should be further investigated in future studies as potential mechanisms underlying enhanced androgen-independent growth of human prostate cancer cells [15].
• OBJECTIVE: The human gene FLRG, identified from a B-cell chronic lymphocytic leukemia bearing a t(11;19) translocation, encodes a secreted glycoprotein highly homologous with follistatin [16].
• Attenuation of bleomycin-induced pulmonary fibrosis by follistatin [17].
• This led us to propose that there may be a relationship between hypoxia and activin A, follistatin and prostaglandin (PG) release from the feto-placental unit [18].

Biological context of FST

• Three FST isoforms have been described that differ in tissue distribution and cell-surface binding activity, suggesting that the FST isoforms and FSTL3 may have some nonoverlapping biological actions [19].
• Production of follistatin protein paralleled the gene expression pattern [20].
• Activin A inhibited the early upregulation of FS secretion when added with BMP-2 and Dex [21].
• To establish the contribution of the FS domains themselves to FS's bioactivity, we prepared mutants with deleted or exchanged domains and intradomain point mutations [22].
• FLRG, an activin-binding protein, is a new target of TGFbeta transcription activation through Smad proteins [23].

Anatomical context of FST

• Follistatin and gremlin were significantly up-regulated in OA chondrocytes but not in OA synovial fibroblasts [20].
• Follistatin and gremlin were expressed preferentially by the chondrocytes at the superficial layers of cartilage [20].
• MATERIALS AND METHODS: In this study, we tested whether the induction of FS secretion might modulate the effects of BMP-2 on osteoblast development, using the bone nodule-forming cultures of fetal rat mandibular cells [21].
• Regulation of follistatin production by rat granulosa cells in vitro [24].
• With respect to the localization of proteins, follistatin was immunolocalized in endometrial epithelial and vascular cells both in tumoral and healthy endometrium without any significant difference in intensity [5].

Associations of FST with chemical compounds

• Tumor necrosis factor alpha and interferon-gamma significantly stimulated follistatin expression but down-regulated expression of gremlin [20].
• Mutation of any of these to Asp or Ala either reduced or eliminated FS bioactivity and disrupted distant epitopes for heparin binding (FS domain 1) or antibody recognition (FS domain 2), suggesting their role in maintaining the conformational integrity of the domain and possibly the FS molecule as a whole [22].
• The cDNA of this new evolutionarily conserved gene (named FLRG for Follistatin-Related Gene) codes for a secreted glycoprotein of the follistatin-module-protein family [25].
• The addition of anti-FS antibody to cultures with BMP-2 and Dex augmented bone nodule formation [21].
• The activin-FS complex in hFF elutes at approximately 200-300 kDa, is immunoprecipitated by anti-hFS288 monoclonal antibodies, and binds to sulfate Cellufine matrix, all characteristics similar to those of recombinant human FS288 [26].
• Our results reveal a key role of GLI2 in activation of the activin/BMP antagonist FST in response to HH signaling and provide new evidence for a regulatory interaction between HH and activin/BMP signaling in hair follicle development and BCC [27].

Physical interactions of FST

• Introduction of the full domain from FS conferred heparin binding to FSTL3, but activin binding was abolished [28].
• A continuous sequence comprising the N-terminal domain and followed by FS domains 1 and 2 fulfills the minimum structural requirement for activin binding and FS bioactivity [22].
• We provide data which show that Follistatin binds BMP-7 and BMP-2 at low affinities and that the binding is reversible [29].

Regulatory relationships of FST

• Activin A stimulated total ir-FS production by undifferentiated and partially differentiated GC, but inhibited total ir-FS production by fully differentiated GC [24].
• Follistatin regulates bone morphogenetic protein-7 (BMP-7) activity to stimulate embryonic muscle growth [29].
• Interestingly, the effect of EGF/TGFalpha could be blocked by cotreatment with follistatin, a potent binding protein for activin, an ovarian growth factor belonging to the TGFbeta superfamily [30].
• Thus, the FST-deficient rat gonadotrope cell is a model that allows for the investigation of factors regulating FSHbeta expression, which might otherwise involve the autocrine/paracrine actions of FST [31].
• Activin A and follistatin influence expression of somatostatin in the ciliary ganglion in vivo [32].

Other interactions of FST

• Differential gene expression and regulation of the bone morphogenetic protein antagonists follistatin and gremlin in normal and osteoarthritic human chondrocytes and synovial fibroblasts [20].
• Levels of marker proteins for differentiation and phosphorylation of similar to mothers against decapentaplegics (Smads) were quantified by Western blot analysis in response to BMP-7, activin A and follistatin [33].
• Measurements Using quantitative reverse transcription polymerase chain reaction (RT-PCR), we investigated the expression of inhibin alpha-, betaA- and betaB-subunits, follistatin, betaglycan, ActRIIA, ActRIIB and Alk-4 in the adrenocortical tissues [34].
• Notably, Ang II, potassium and aldosterone decreased mRNA levels of follistatin that extracellularly neutralizes bioactivities of activins and BMPs although the BMP-6 receptor expression was unaffected [35].
• The dendrite-promoting activity of BMP-5 is significantly inhibited by the BMP antagonists noggin and follistatin and by a BMPR-IA-Fc chimeric protein [36].

Analytical, diagnostic and therapeutic context of FST

• Follistatin protein production was measured using a specific enzyme-linked immunosorbent assay, and localization of follistatin and gremlin in cartilage was determined by immunohistochemical analysis [20].
• Mutants were expressed from mammalian (Chinese hamster ovary) cells and evaluated for activin binding and for biological activity in assays measuring differing aspects of FS bioactivity: activin-mediated transcriptional activity and suppression of FSH secretion in primary pituitary cell cultures [22].
• METHODS: Expression levels of follistatin, follistatin-like 3, and activin subunits beta(A) as well as beta(E) were investigated in chemically induced rat and human liver tumours by real-time PCR and immunohistochemistry [2].
• Using enhanced resolution gel filtration, immunoprecipitation with monoclonal antibodies to rhFS288, and sulfated carbohydrate binding, activin-FS complexes in hFF and serum differed [26].
• In the present study we analyzed the splicing variants of FS mRNAs in fibroblasts from genital and nongenital skin by RT-PCR and northern analysis, and examined the induction of FS mRNA and protein by hormones and growth factors in skin fibroblasts from human and nonhuman primates [37].

References