Fibroblast growth factors, their receptors and signaling.
TL;DR: FGF signaling also appears to play a role in tumor growth and angiogenesis, and autocrine FGF signaling may be particularly important in the progression of steroid hormone-dependent cancers to a hormone-independent state.
Abstract: Fibroblast growth factors (FGFs) are small polypeptide growth factors, all of whom share in common certain structural characteristics, and most of whom bind heparin avidly. Many FGFs contain signal peptides for secretion and are secreted into the extracellular environment, where theycan bind to the heparan-like glycosaminoglycans (HLGAGs) of the extracellular matrix (ECM). From this reservoir, FGFs mayact directlyon target cells, or theycan be released through digestion of the ECM or the activityof a carrier protein, a secreted FGF binding protein. FGFs bind specific receptor tyrosine kinases in the context of HLGAGs and this binding induces receptor dimerization and activation, ultimatelyresulting in the activation of various signal transduction cascades. Some FGFs are potent angiogenic factors and most playimportant roles in embry onic development and wound healing. FGF signaling also appears to playa role in tumor growth and angiogenesis, and autocrine FGF signaling maybe particularlyimportant in the progression of steroid hormone-dependent cancers to a hormone-independent state.
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TL;DR: This review provides an overview of current approaches in craniofacial surgery for treating states of bone excess and deficit, recent advances in the understanding of the molecular and cellular processes underlying craniosynostosis, a pathological state ofBone excess, and current research efforts in cellular-based therapies for bone regeneration.
Abstract: Objectives
As a surgical subspecialty devoted to restoration of normal facial and calvarial anatomy, craniofacial surgeons must navigate the balance between pathologic states of bone excess and bone deficit. While current techniques employed take root in lessons learned from the success and failure of early pioneers, craniofacial surgery continues to evolve, and novel modalities will undoubtedly arise integrating past and present experiences with future promise to effectively treat craniofacial disorders.
9 citations
Cites background from "Fibroblast growth factors, their re..."
...The FGF signal transduction machinery has been found to employ several components of the Mitogen-Activated Protein Kinase (MAPK) pathway, allowing the ability to potentially manipulate FGF signaling through cytoplasmic intermediaries [73]....
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...Multiple reports have demonstrated FGF signal transduction to occur through ligand-induced receptor homo- and heterodimerization activating intracellular tyrosine kinase domains [73]....
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TL;DR: FGF2-mediated activation of FGFRs may promote a switch in transcriptional profile of ovine ICM from EPI- to hypoblast-associated gene expression, which isomersally important for ovine embryo development.
Abstract: Fibroblast growth factors (FGFs) and their receptors (FGFRs) are increasingly recognized as important regulators of embryo development in mammals. This study investigated the importance of FGF signaling during in vitro development of ovine embryo. The mRNAs of four FGFR subtypes were detected throughout preimplantation development of in vitro fertilized (IVF) embryos, peaked in abundance at the morula stage, and decreased significantly at the blastocyst stage. To gain insight into the role of these mRNAs in embryo development, IVF embryos were cultured in the presence of FGF2 (100 or 500 ng/ml: beginning from days 1 or 4 to 7) or PD173074 (1 µM: beginning from days 1 to 7) as usual treatments for activation or inhibition of FGFRs, respectively. FGF2-supplementation did not affect the percentage of embryos that developed to the blastocyst, blastocyst cell count and the proportion of cells allocated in inner cell mass (ICM) and trophectoderm (TE) compared to control (p > 0.05). Also, increasing the dosage or duration of FGF2 treatment did not significantly alter blastocyst yield or differential cell count (p > 0.05). PD173074-mediated inhibition of FGFRs did not significantly affect blastocyst yield (p > 0.05). Assessment of expression profiles of lineage-associated markers revealed that FGF2 (500 ng/ml) supplementation: (i) significantly increased expression of putative hypoblast marker (GATA4), (ii) significantly decreased expression of putative epiblast (EPI) marker (NANOG) and (iii) did not change TE markers (CDX2 and IFNT) and pluripotency makers (OCT4, SOX2 and REX1). In summary, FGF2-mediated activation of FGFRs may promote a switch in transcriptional profile of ovine ICM from EPI- to hypoblast-associated gene expression.
9 citations
Cites background from "Fibroblast growth factors, their re..."
...Therefore, each FGFR exhibits specific binding affinity to more than one FGF (Johnson et al., 1991; Ornitz et al., 1996; Powers et al., 2000)....
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TL;DR: BFGF supplementation enhances stem cell marker expression in DMSCs, however, the role of bFGF on osteogenic differentiation by D MSCs remains controversial.
Abstract: Background: Basic fibroblast growth factor (bFGF) plays a crucial role in various biological processes, including cell growth, survival, migration, and differentiation. In stem cell biology, bFGF is employed to maintain stemnessand regulate differentiation. Objectives: To review the role of bFGF in the behavior of stem cells, focusing particularly on human dental tissue-derived mesenchymal stem cells (DMSCs). Methods: The articles from January 1, 1990 to March 25, 2015 in the PubMed database were searched with assigned key words (dental stem cells and (bFGF or FGF2)). Titles and abstracts of the retrieved articles wereevaluated to identify inclusion criteria. Results: Sixty-five articles were identified from the PubMed database using the assigned keywords. Eighteen articles met the inclusion criteria including: (1) articles published in English, (2) articles describing the effects ofendogenous and exogenous bFGF in cell culture and animal studies, and (3) the cell model used in the study was derived from dental-related tissues, and were employed as the main articles discussed in the present narrative review. Conclusion: bFGF supplementation enhances stem cell marker expression in DMSCs. However, the role of bFGF on osteogenic differentiation by DMSCs remains controversial. Keywords: Basic fibroblast growth factor, dental tissue-derived stem cells, differentiation, stemness
9 citations
TL;DR: This review aims to investigate the role of cytokines in modulating vocal fold fibrosis by investigating their role in the establishment of VF fibrosis.
Abstract: OBJECTIVES Vocal fold (VF) scarring and laryngeal stenosis are a significant clinical challenge. Excessive scar formation causes low voice quality or even life-threatening obstructions. Cytokines are thought to modulate multiple steps of the establishment of VF fibrosis, but there is no systematic report regarding their role in modulating VF fibrosis. This review aims to investigate the role of cytokines in modulating vocal fold fibrosis. STUDY DESIGN Literature review. METHODS This review searched for all relevant peer publications in English for the period 2009 to 2019 in the PubMed database using search terms: "laryngeal stenosis," "vocal fold scarring," and "cytokines." A thorough investigation of the methods and results of the reviewed studies was performed. RESULTS Comprehensive research in various studies, including analyses of prostaglandin E2 (PGE2), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), transforming growth factor-β3 (TGF-β3), and interleukin-10 (IL-10), supports cytokine therapy for VF scarring and laryngeal stenosis to some extent. A few clinical studies on this topic support the conclusion that HGF and bFGF can be selected as effective drugs, and no serious side effects were found. CONCLUSIONS This review describes the potential of cytokines for modulating the process of VF fibrogenesis, although cytokines are still an unproven treatment method. As no ideal drugs exist, cytokines may be considered the candidate treatment for preventing VF fibrogenesis. Laryngoscope, 131:139-145, 2021.
9 citations
TL;DR: Overall genetic variation in FGF2 does not appear to play a role in susceptibility to ovarian cancer, and common single nucleotide polymorphisms in the FGF1 gene may alter angiogenic potential and thereby susceptibility to Ovarian cancer.
Abstract: Fibroblast growth factor (FGF)-2 (basic) is a potent angiogenic molecule involved in tumor progression, and is one of several growth factors with a central role in ovarian carcinogenesis. We hypothesized that common single nucleotide polymorphisms (SNPs) in the FGF2 gene may alter angiogenic potential and thereby susceptibility to ovarian cancer. We analyzed 25 FGF2 tgSNPs using five independent study populations from the United States and Australia. Analysis was restricted to non-Hispanic White women with serous ovarian carcinoma (1269 cases and 2829 controls). There were no statistically significant associations between any FGF2 SNPs and ovarian cancer risk. There were two nominally statistically significant associations between heterozygosity for two FGF2 SNPs (rs308379 and rs308447; p < .05) and serous ovarian cancer risk in the combined dataset, but rare homozygous estimates did not achieve statistical significance, nor were they consistent with the log additive model of inheritance. Overall genetic variation in FGF2 does not appear to play a role in susceptibility to ovarian cancer.
9 citations
References
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TL;DR: It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF.
2,448 citations
TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.
Abstract: Communication between cells assumes particular importance in multicellular organisms. The growth, migration and differentiation of cells in the embryo, and their organization into specific tissues, depend on signals transmitted from one cell to another. In the adult, cell signalling orchestrates normal cellular behaviour and responses to wounding and infection. The consequences of breakdowns in this signalling underlie cancer, diabetes and disorders of the immune and cardiovascular systems. Conserved protein domains that act as key regulatory participants in many of these different signalling pathways are highlighted.
2,433 citations
"Fibroblast growth factors, their re..." refers background in this paper
...One way these recruited target proteins may be localized to the activated receptor is through the interaction between their Src-homology 2 (SH2) domains and specific phosphotyrosine residues on the activated receptor (Pawson 1995)....
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...Phosphorylated tyrosine residues, in turn, recruit other signaling molecules to the activated receptors and propagate the signal through many possible transduction pathways (Pawson 1995)....
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TL;DR: Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of Thalidomid-treated embryos.
Abstract: Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.
2,364 citations
TL;DR: It is demonstrated that FGF 1 is the only FGF that can activate all FGF receptor splice variants and the relative activity of all the other members of the FGF family is determined.
2,066 citations
"Fibroblast growth factors, their re..." refers background in this paper
...†From Ornitz et al. (1996), except where stated; ‡From Koga et al. (1995); §From Miralles et al. (1999); ¶From Xu et al. (1999). topologically identical to interleukin-1β (IL-1β) (Zhu et al. 1991), with which some members also share the feature of secretion by an endoplasmic reticulum…...
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...Mutation of all four cysteines to serines results in a protein with the same secondary structure and equally mitogenic for 3T3 cells as the wild-type FGF-2 (Foxet al. 1988), suggesting that the formation of disulfide bridges is not important for the secondary structure and mitogenic activity of…...
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...Ornitz et al. (1996) determined the specificity of different FGFs for different receptor isoforms by overexpressing these isoforms in Baf3 cells, which do not normally express FGFRs, and assaying for [3H]thymidine incorporation in these cells following treatment with different FGFs (see Table 2)....
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...1, IIIb 100 60 34 16 4 5 6 4 4 1, IIIc 100 104 0 102 59 55 0 1 21 2, IIIb 100 9 45 15 5 5 81 4 7 2, IIIc 100 64 4 94 25 61 2.5 16 89 3, IIIb 100 1 2 1 1 1 1 1 42 3, IIIc 100 107 1 69 12 9 1 41 96 4 100 113 6 108 7 79 2 76 75 Modified from Ornitz et al. (1996)....
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1,994 citations
"Fibroblast growth factors, their re..." refers background in this paper
...Defining features of the FGF family are a strong affinity for heparin and HLGAGs (Burgess & Maciag 1989), as well as a central core of 140 amino acids that is highly homologous between different family members....
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