Fibroblast Growth Factor Signaling in Lung Development and Disease

Fibroblast growth factors (FGFs), a large group of polypeptide growth factors, have key roles in lung biology. FGFs can be organized into seven sub-families based on conserved amino acid sequence and gene structure. FGFs have a high affinity for heparin and heparan sulfate (H/HS), which retain FGFs in the extracellular matrix and on the cell surface. H/HS also function as essential co-factors for FGF binding and activation of one of four polypeptide tyrosine kinase receptors (FGFRs). The chemical heterogeneity of HS and alternative splicing of FGFRs determines binding specificity and kinetics of receptor activation. FGF signaling affects cell proliferation, cell survival, chemotaxis, migration, and cell adhesion. In the lung, FGFs function during specific stages of development, homeostasis, and response to injury. FGFs also have specific roles in lung cancer, pulmonary fibrosis, and protection against DNA damage induced by oxidants and some environmental toxicants.