Fibroblast growth factors, their receptors and signaling.

doi:10.1677/ERC.0.0070165

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Fibroblast growth factors, their receptors and signaling.

Journal Article•DOI•

Fibroblast growth factors, their receptors and signaling.

Ciaran Powers¹, S W McLeskey, Anton Wellstein¹•Institutions (1)

Georgetown University¹

01 Sep 2000-Endocrine-related Cancer (Bioscientifica Ltd)-Vol. 7, Iss: 3, pp 165-197

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.

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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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Journal Article•DOI•

Identification of metabolic pathways underlying FGF1 and CHIR99021-mediated cardioprotection

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Bing Li Lipeng Han Lin Li Zhenbo Xu, Fan Li, Wenjing Zhang, Yajuan Su, Ling Tang, Pengsheng Li, Jyotsna Joshi, Aaron Yang, Dong Li, Zhao Wang, Shu Wang, J. Xie, Haiwei Gu, Wuqiang Zhu - Show less +10 more

01 May 2022-iScience

TL;DR: Heusch et al. as discussed by the authors showed that FGF1/CHIR99021 nanofibers enhanced the heart capacity to utilize glycolysis as an energy source and reduced the accumulation of branched-chain amino acids in ischemic myocardium.

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3 citations

Journal Article•DOI•

Effects of PDGF-BB and b-FGF on the production of cytokines, hyaluronic acid and the proliferation of orbital fibroblasts in thyroid ophthalmopathy

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Sung Mo Kang¹, So Yeon Lee¹•Institutions (1)

Inha University¹

18 Jul 2013-Molecular & Cellular Toxicology

TL;DR: PDGF-BB and b-FGF induced orbital fibroblasts increased production of hyaluronic acid in thyroid-associated ophthalmopathy and increased the production of IL-8, which can be incorporated into DNA during active DNA synthesis.

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Abstract: The effects of Platelet-derived growth factor-BB(PDGF-BB) and Basic-fibroblast growth factor (b-FGF) on the proliferation and production of hyaluronic acid and, cytokine productions in cultured human orbital fibroblasts were evaluated. Orbital fibroblasts were cultured (5 from eyes with thyroid-associated ophthalmopathy and, 5 from normal eyes) and classified into 3 groups-: (1) the Unstimulated group, (2) the Platelet-derived growth factor-BB stimulation group and, (3) the b-Fibroblast growth factor stimulation group. The hyaluronic acid concentration of each group was measured by ELISA. The cytokine production (IL-1β, IL-2, IL-6, IL-8 and RANTES) of each group was measured in the cultured medium. The proliferation of orbital fibroblasts was measured in each group using a thymidine analog EdU, which can be incorporated into DNA during active DNA synthesis. In conclusion, PDGF-BB and b-FGF induced orbital fibroblasts increased production of hyaluronic acid in thyroid-associated ophthalmopathy. In addition to the induction of orbital fibroblast proliferation, PDGF-BB increased the production of IL-8. Further studies on the inhibitory factors of orbital fibroblasts with a larger sample size are warranted to aid in the development of fundamental treatments for thyroid-associated ophthalmopathy.

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3 citations

Fibroblast Growth Factor Signaling in Prostate Stem Cells and Prostate Cancer

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Yanqing Huang

10 Aug 2015

3 citations

Cites background from "Fibroblast growth factors, their re..."

...that vary in both extracellular ligand-binding and the intracellular kinase domains (62,63)....
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Start small, think big: Growth monitoring, genetic analysis, treatment and quality of life in children with growth disorders

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S.E. Stalman

01 Jan 2016

TL;DR: The translation process and psychometric testing of the original European Quality of Life in Short Stature Youth (QoLISSY) questionnaire, developed to evaluate the health-related QoL in short children, is described.

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Abstract: The aim of this thesis is to focus on issues that arise when dealing with children with growth disorders – from growth monitoring and genetic analysis to treatment effects on growth and quality of life. The first part of this thesis focuses on guidelines for diagnostic workup of children with growth disorders, including either growth failure or overgrowth. First, we retrospectively investigated the sensitivity and specificity of guidelines for diagnostic workup currently used in the Netherlands, Finland and the UK in a Dutch cohort of children aged 3 to 10 years with growth failure (Chapter 2). Second, in Chapter 3 we performed a similar study in adolescents, taking into account the influence of puberty on growth. Third, we investigated the diagnostic workup and follow-up in children with tall stature (Chapter 4). In the second part of this thesis we performed genetic analyses in small for gestational age (SGA) newborns. In Chapter 5 we present our study investigating SGA newborns, using a combination of array-CGH, genome wide methylation array and whole exome sequencing (WES). Part three of the thesis focuses on treatment of short children. We investigated the effect of growth hormone treatment in patients with maternal uniparental disomy of chromosome 14 in Chapter 6. The final part of this thesis describes the translation process and psychometric testing of the original European Quality of Life in Short Stature Youth (QoLISSY) questionnaire, developed to evaluate the health-related QoL in short children, as presented in Chapter 7.

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3 citations

Cites background from "Fibroblast growth factors, their re..."

...GGT1 is associated with growth retardation in mice [46] and FGF8 is a member of the fibroblast growth factors, which play an important role in the regulation of embryonic development, cell proliferation, cell differentiation [47] and bone formation [48, 49]....
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...Regarding growth hormone therapy, on average 10-14 cm height gain can be expected after treatment in children with in growth hormone deficiency (GHD) [46], 5-8 cm in Turner syndrome [47] and 3-6 cm in idiopathic short stature (ISS) [48, 49]....
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Dissertation•

Evaluation of mRNA/ Gene Expression of Pro-Angiogenic Factors – Ang 1, Ang 2 and HGF in Periodontal Health and Disease

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R S Keerthiha

01 Apr 2017

TL;DR: The constitutive expression of Ang 1, Ang 2 and HGF proangiogenic factors in the gingival tissues of periodontal health reaffirms their role inperiodontal homeostasis, while their dysregulation in periodontAL disease suggests a potential pathogenic role.

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Abstract: BACKGROUND : Inflammation of the gingiva is a hallmark clinical sign for the initiation of chronic periodontal disease. Angiogenesis plays a vital role in the formation of new blood cells and in the recruitment of inflammatory cells to the site of disease progression, thereby exhibiting a close link between inflammation in chronic and acute inflammatory periodontal diseases. It has been proven over years that the process of angiogenesis initiates with the presence of proangiogenic factors that stimulates the formation of microcapillary vessels. It is evident that proangiogenic cytokines Ang 1, Ang 2 and HGF play an important role in the inflammation and in the process of remodeling in periodontal tissues. This study aims to evaluate the mRNA/ gene expression of Ang 1, Ang 2 and HGF proangiogenic factors in periodontally healthy individuals and in patients with chronic periodontitis. MATERIALS AND METHODS : 20 gingival samples were obtained from each group of patients (Group A: periodontal health; Group B: periodontal disease). The samples were then evaluated for the expression of mRNAs of Ang 1, Ang 2 and HGF by real time reverse transcription polymerase chain reaction (Q RT-PCR). RESULTS : The results of our present study demonstrated an up regulation in the expression Ang 1 and HGF gene in the diseased samples and a down regulation in the expression of Ang 2 gene in diseased samples which was statistically insignificant (p=0.129, p=0.934 and p= 0.899) for Ang 1, Ang 2 and HGF respectively. CONCLUSION : To conclude the constitutive expression of Ang 1, Ang 2 and HGF proangiogenic factors in the gingival tissues of periodontal health reaffirms their role in periodontal homeostasis, while their dysregulation in periodontal disease suggests a potential pathogenic role. Further studies targeted towards mechanism of action are required to elicit their exact role in the etiopathogenesis of periodontal disease.

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3 citations

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Journal Article•DOI•

Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.

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Avner Yayon¹, Michael Klagsbrun², Jeffrey D. Esko³, Philip Leder⁴, David M. Ornitz⁴ - Show less +1 more•Institutions (4)

Weizmann Institute of Science¹, Harvard University², University of Alabama at Birmingham³, Howard Hughes Medical Institute⁴

22 Feb 1991-Cell

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.

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2,448 citations

Journal Article•DOI•

Protein modules and signalling networks

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Tony Pawson¹•Institutions (1)

Mount Sinai Hospital, Toronto¹

16 Feb 1995-Nature

TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.

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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.

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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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Journal Article•DOI•

Thalidomide is an inhibitor of angiogenesis.

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Robert J. D'Amato¹, Michael S. Loughnan, Evelyn Flynn, Judah Folkman•Institutions (1)

Harvard University¹

26 Apr 1994-Proceedings of the National Academy of Sciences of the United States of America

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.

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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.

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2,364 citations

Journal Article•DOI•

Receptor specificity of the fibroblast growth factor family.

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David M. Ornitz¹, Jingsong Xu¹, Jennifer S. Colvin¹, Donald G. McEwen¹, Craig A. MacArthur¹, François Coulier², Guangxia Gao³, Mitchell Goldfarb⁴ - Show less +4 more•Institutions (4)

Washington University in St. Louis¹, French Institute of Health and Medical Research², Columbia University³, Icahn School of Medicine at Mount Sinai⁴

21 Jun 1996-Journal of Biological Chemistry

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.

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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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Journal Article•DOI•

The heparin-binding (fibroblast) growth factor family of proteins.

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Wilson H. Burgess, Thomas Maciag

01 Jan 1989-Annual Review of Biochemistry

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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