title: Growth factors in cystic fibrosis - when more is not enough.
abstract: In the airways of patients with cystic fibrosis, repeated cycles of infection and inflammation are responsible for bronchial wall thickening, a major determinant of loss of FEV(1) and progressive damage to the small and large airways. Proteolytic degradation of elastin, collagen and fibronectin fibrils in the tissue matrix leads to the loss of normal tissue architecture and the development of bronchiectasis, the most commonly observed morphological change on high-resolution computed tomography examination. We have reviewed the evidence for increased expression of growth factors (TGF, HGF, FGF, EGF, VEGF) and activation of tissue repair processes in cystic fibrosis. Significantly higher concentrations of the growth factors compared with normal do not appear to prevent or reverse structural remodelling in the airways. The reasons why this process appears to be ineffective are discussed and we speculate on alternative strategies that might have a significant impact on the observed structural changes.
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK. jan.shute@port.ac.uk
authors.forename: Janis
authors.initials: J
authors.lastname: Shute
authors.forename: Lindsay
authors.initials: L
authors.lastname: Marshall
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bodey
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
mesh_terms: D003550:Cystic Fibrosis / Q000378:metabolism / Q000503:physiopathology*; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000502:physiology; D006133:Growth Substances / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D019272:Leukocyte Elastase / Q000502:physiology; D008222:Lymphokines / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; C496453:FGF7 protein, human; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D019272:Leukocyte Elastase