New developments in the biology of fibroblast growth factors

Ornitz, David M.; Itoh, Nobuyuki

doi:10.1002/wsbm.1549

Cited by 78 publications

(87 citation statements)

References 1,566 publications

(2,214 reference statements)

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“…An FGF can bind to multiple FGFRs. FGFs rely on heparan sulfate proteoglycan (HSPG) and Klotho-type coreceptors to improve their binding to FGFRs (Ornitz and Itoh, 2022). After FGF-FGFR binding, through the autophosphorylation of FGFRs, with the help of FGFR substrate 2 and PLCγ, signals are transferred to the RAS-ERK, PI3K/AKT, PKC, and JAK-STAT signaling cascades, which mediate the survival, proliferation, differentiation, or migration of cells (Inomata et al, 2015;Katoh, 2018).…”

Section: Fibroblast Growth Factormentioning

confidence: 99%

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Liu

et al. 2022

Front. Pharmacol.

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Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown origin that usually results in death from secondary respiratory failure within 2–5 years of diagnosis. Recent studies have identified key roles of cytokine and growth factor pathways in the pathogenesis of IPF. Although there have been numerous clinical trials of drugs investigating their efficacy in the treatment of IPF, only Pirfenidone and Nintedanib have been approved by the FDA. However, they have some major limitations, such as insufficient efficacy, undesired side effects and poor pharmacokinetic properties. To give more insights into the discovery of potential targets for the treatment of IPF, this review provides an overview of cytokines, growth factors and their signaling pathways in IPF, which have important implications for fully exploiting the therapeutic potential of targeting cytokine and growth factor pathways. Advances in the field of cytokine and growth factor pathways will help slow disease progression, prolong life, and improve the quality of life for IPF patients in the future.

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Section: Fibroblast Growth Factormentioning

confidence: 99%

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Liu

et al. 2022

Front. Pharmacol.

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“…Multiple secreted proteins in the lung, including cytokines and growth factors, can regulate virus infection, the inflammatory response, and post-infection repair to combat severe IAV disease. Fibroblast growth factors (FGFs) are a family of secreted proteins that regulate tissue maintenance, metabolism, regeneration, and repair of adult tissues by binding to the extracellular domain of four transmembrane tyrosine kinase FGF receptors (FGFRs) [ 5 , 6 ]. In the developing lung, FGF1, FGF2, FGF3, FGF7, FGF9, FGF10, and FGF18 all perform essential regulatory functions mediating organogenesis [ 7 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor-9 expression in airway epithelial cells amplifies the type I interferon response and alters influenza A virus pathogenesis

et al. 2022

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Influenza A virus (IAV) preferentially infects conducting airway and alveolar epithelial cells in the lung. The outcome of these infections is impacted by the host response, including the production of various cytokines, chemokines, and growth factors. Fibroblast growth factor-9 (FGF9) is required for lung development, can display antiviral activity in vitro, and is upregulated in asymptomatic patients during early IAV infection. We therefore hypothesized that FGF9 would protect the lungs from respiratory virus infection and evaluated IAV pathogenesis in mice that overexpress FGF9 in club cells in the conducting airway epithelium (FGF9-OE mice). However, we found that FGF9-OE mice were highly susceptible to IAV and Sendai virus infection compared to control mice. FGF9-OE mice displayed elevated and persistent viral loads, increased expression of cytokines and chemokines, and increased numbers of infiltrating immune cells as early as 1 day post-infection (dpi). Gene expression analysis showed an elevated type I interferon (IFN) signature in the conducting airway epithelium and analysis of IAV tropism uncovered a dramatic shift in infection from the conducting airway epithelium to the alveolar epithelium in FGF9-OE lungs. These results demonstrate that FGF9 signaling primes the conducting airway epithelium to rapidly induce a localized IFN and proinflammatory cytokine response during viral infection. Although this response protects the airway epithelial cells from IAV infection, it allows for early and enhanced infection of the alveolar epithelium, ultimately leading to increased morbidity and mortality. Our study illuminates a novel role for FGF9 in regulating respiratory virus infection and pathogenesis.

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“…In line with these pieces of evidence, Kuslak and colleagues [26] have demonstrated that the spontaneous mouse SV shape (svs) mutation, which affects budding/branching of the SV is caused by a mutation of the Fgfr2 gene that perturbs splicing of the gene. Authors also show that the alternative splice isoform Fgfr2c, whose cognate ligands are FGF7 and FGF10 [28], is the main isoform expressed in the SV [26]. Previous work has shown that both FGF7 (also known as KGF) and FGF10 are expressed in the mesenchyme surrounding SVs during development and, as mentioned earlier, that both factors can promote SV branching in vitro [18,19].…”

Section: Discussionmentioning

confidence: 70%

A dominant negative mutation uncovers cooperative control of caudal Wolffian duct development by Sprouty genes

Altés

Vaquero

Cuesta

et al. 2022

Cell. Mol. Life Sci.

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The Wolffian ducts (WD) are paired epithelial tubules central to the development of the mammalian genitourinary tract. Outgrowths from the WD known as the ureteric buds (UB) generate the collecting ducts of the kidney. Later during development, the caudal portion of the WD will form the vas deferens, epididymis and seminal vesicle in males, and will degenerate in females. While the genetic pathways controlling the development of the UB are firmly established, less is known about those governing development of WD portions caudal to the UB. Sprouty proteins are inhibitors of receptor tyrosine kinase (RTK) signaling in vivo. We have recently shown that homozygous mutation of a conserved tyrosine (Tyr53) of Spry1 results in UB defects indistinguishable from that of Spry1 null mice. Here, we show that heterozygosity for the Spry1 Y53A allele causes caudal WD developmental defects consisting of ectopically branched seminal vesicles in males and persistent WD in females, without affecting kidney development. Detailed analysis reveals that this phenotype also occurs in Spry1+/– mice but with a much lower penetrance, indicating that removal of tyrosine 53 generates a dominant negative mutation in vivo. Supporting this notion, concomitant deletion of one allele of Spry1 and Spry2 also recapitulates the genital phenotype of Spry1Y53A/+ mice with high penetrance. Mechanistically, we show that unlike the effects of Spry1 in kidney development, these caudal WD defects are independent of Ret signaling, but can be completely rescued by lowering the genetic dosage of Fgf10. In conclusion, mutation of tyrosine 53 of Spry1 generates a dominant negative allele that uncovers fine-tuning of caudal WD development by Sprouty genes.

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New developments in the biology of fibroblast growth factors

Cited by 78 publications

References 1,566 publications

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Fibroblast growth factor-9 expression in airway epithelial cells amplifies the type I interferon response and alters influenza A virus pathogenesis

A dominant negative mutation uncovers cooperative control of caudal Wolffian duct development by Sprouty genes

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