New Developments in the Biology of Fibroblast Growth Factors

Overview

Journal WIREs Mech Dis

Specialties Biology
Biomedical Engineering
Genetics
Physiology

Date 2022 Feb 10

PMID 35142107

Authors

David M Ornitz

Nobuyuki Itoh

Affiliations

Soon will be listed here.

Abstract

The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltage-gated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases. This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology Congenital Diseases > Stem Cells and Development Cancer > Stem Cells and Development.

Citing Articles

Effects of Interleukin-6 (IL-6) on In Vitro Cultured Equine Chorionic Girdle Cells.

Mu S, Shen Y, Ren H, Ulaangerel T, Yi M, Zhao B Animals (Basel). 2025; 15(3).

PMID: 39943220 PMC: 11816123. DOI: 10.3390/ani15030450.

FGF-based drug discovery: advances and challenges.

Chen G, Chen L, Li X, Mohammadi M Nat Rev Drug Discov. 2025; .

PMID: 39875570 DOI: 10.1038/s41573-024-01125-w.

The Crosstalk Between Cartilage and Bone in Skeletal Growth.

Hernandez-Garcia F, Fernandez-Iglesias A, Rodriguez Suarez J, Gil Pena H, Lopez J, Perez R Biomedicines. 2025; 12(12.

PMID: 39767569 PMC: 11727353. DOI: 10.3390/biomedicines12122662.

Less, but More: New Insights From Appendicularians on Chordate Fgf Evolution and the Divergence of Tunicate Lifestyles.

Sanchez-Serna G, Badia-Ramentol J, Bujosa P, Ferrandez-Roldan A, Torres-Aguila N, Fabrega-Torrus M Mol Biol Evol. 2024; 42(1).

PMID: 39686543 PMC: 11733497. DOI: 10.1093/molbev/msae260.

FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases.

Stefanova D, Olszewski D, Glitscher M, Bauer M, Ferrarese L, Wust D Cell Mol Life Sci. 2024; 81(1):471.

PMID: 39621133 PMC: 11612106. DOI: 10.1007/s00018-024-05502-x.

References

Lu H, Jia C, Wu D, Jin H, Lin Z, Pan J . Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway. Cell Death Dis. 2021; 12(10):865. PMC: 8460788. DOI: 10.1038/s41419-021-04157-x. View

Zhang X, Ibrahimi O, Olsen S, Umemori H, Mohammadi M, Ornitz D . Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006; 281(23):15694-700. PMC: 2080618. DOI: 10.1074/jbc.M601252200. View

Chang M, Lin H, Fu H, Wang B, Han G, Fan M . MicroRNA-195-5p Regulates Osteogenic Differentiation of Periodontal Ligament Cells Under Mechanical Loading. J Cell Physiol. 2017; 232(12):3762-3774. DOI: 10.1002/jcp.25856. View

Chen H, Li J, Zhang D, Zhou X, Xie J . Role of the fibroblast growth factor 19 in the skeletal system. Life Sci. 2020; 265:118804. DOI: 10.1016/j.lfs.2020.118804. View

Musgrove J, Wolf M . Regulation and Effects of FGF23 in Chronic Kidney Disease. Annu Rev Physiol. 2019; 82:365-390. DOI: 10.1146/annurev-physiol-021119-034650. View

Chen J, Hu J, Liu H, Xiong Y, Zou Y, Huang W . FGF21 Protects the Blood-Brain Barrier by Upregulating PPARγ via FGFR1/β-klotho after Traumatic Brain Injury. J Neurotrauma. 2018; 35(17):2091-2103. DOI: 10.1089/neu.2017.5271. View

Lebowitz E, Orbach M, Marin C, Salmaso N, Vaccarino F, Silverman W . Fibroblast Growth Factor 2 Implicated in Childhood Anxiety and Depression Symptoms. J Affect Disord. 2021; 282:611-616. PMC: 7897422. DOI: 10.1016/j.jad.2020.12.055. View

Gallegos T, Kamei C, Rohly M, Drummond I . Fibroblast growth factor signaling mediates progenitor cell aggregation and nephron regeneration in the adult zebrafish kidney. Dev Biol. 2019; 454(1):44-51. PMC: 6717540. DOI: 10.1016/j.ydbio.2019.06.011. View

Rohmann E, Brunner H, Kayserili H, Uyguner O, Nurnberg G, Lew E . Mutations in different components of FGF signaling in LADD syndrome. Nat Genet. 2006; 38(4):414-7. DOI: 10.1038/ng1757. View

10.

Morgani S, Metzger J, Nichols J, Siggia E, Hadjantonakis A . Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning. Elife. 2018; 7. PMC: 5807051. DOI: 10.7554/eLife.32839. View

11.

Zakrzewska M, Opalinski L, Haugsten E, Otlewski J, Wiedlocha A . Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling. Int J Mol Sci. 2019; 20(8). PMC: 6514807. DOI: 10.3390/ijms20081826. View

12.

Frank D, Penkala I, Zepp J, Sivakumar A, Linares-Saldana R, Zacharias W . Early lineage specification defines alveolar epithelial ontogeny in the murine lung. Proc Natl Acad Sci U S A. 2019; 116(10):4362-4371. PMC: 6410851. DOI: 10.1073/pnas.1813952116. View

13.

Korsensky L, Ron D . Regulation of FGF signaling: Recent insights from studying positive and negative modulators. Semin Cell Dev Biol. 2016; 53:101-14. DOI: 10.1016/j.semcdb.2016.01.023. View

14.

Naski M, Colvin J, Coffin J, Ornitz D . Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3. Development. 1998; 125(24):4977-88. DOI: 10.1242/dev.125.24.4977. View

15.

Pal S, Rosenberg J, Hoffman-Censits J, Berger R, Quinn D, Galsky M . Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with Alterations. Cancer Discov. 2018; 8(7):812-821. PMC: 6716598. DOI: 10.1158/2159-8290.CD-18-0229. View

16.

Gong S . Isoforms of receptors of fibroblast growth factors. J Cell Physiol. 2014; 229(12):1887-95. DOI: 10.1002/jcp.24649. View

17.

Moosa S, Wollnik B . Altered FGF signalling in congenital craniofacial and skeletal disorders. Semin Cell Dev Biol. 2015; 53:115-25. DOI: 10.1016/j.semcdb.2015.12.005. View

18.

Lander R, Petersen C . Wnt, Ptk7, and FGFRL expression gradients control trunk positional identity in planarian regeneration. Elife. 2016; 5. PMC: 4865369. DOI: 10.7554/eLife.12850. View

19.

Owall L, Kreiborg S, Duno M, Hermann N, Darvann T, Hove H . Phenotypic variability in Muenke syndrome-observations from five Danish families. Clin Dysmorphol. 2019; 29(1):1-9. DOI: 10.1097/MCD.0000000000000300. View

20.

Liu L, Song C, Li J, Wang Q, Zhu M, Hu Y . Fibroblast growth factor 10 alleviates particulate matter-induced lung injury by inhibiting the HMGB1-TLR4 pathway. Aging (Albany NY). 2020; 12(2):1186-1200. PMC: 7053597. DOI: 10.18632/aging.102676. View