title: Aberrant fibrillin-1 expression in early emphysematous human lung: a proposed predisposition for emphysema.
abstract: Parenchymal destruction, airspace enlargement, and loss of elasticity are hallmarks of pulmonary emphysema. Although the basic mechanism is unknown, there is a consensus that malfunctioning of the extracellular matrix is a major contributor to the pathogenesis of emphysema. In this study, we analyzed the expression of the elastic fiber protein fibrillin-1 in a large number (n=69) of human lung specimens with early-onset emphysema. Specimens were morphologically characterized by the Destructive Index, the Mean Linear Intercept, and the Panel Grading. We observed a strong correlation (P<0.001) of aberrant fibrillin-1 staining with the degree of destruction of lung parenchyma (r=0.71), airspace enlargement (r=0.47), and emphysema-related morphological abnormalities (r=0.69). There were no obvious correlations with age and smoking behavior. Staining for three other extracellular matrix components (type I collagen, type IV collagen, and laminin) was not affected. The aberrant fibrillin-1 staining observed in this study is similar to that observed in Marfan syndrome, a syndrome caused by mutations in the gene encoding fibrillin-1. Strikingly, emphysema is noticed in a number of Marfan patients. This, together with the notion that disruption of the fibrillin-1 gene in mice results in emphysematous lesions, makes fibrillin-1 a strong candidate to be involved in the etiology and pathogenesis of emphysema.
authors: Department of Biochemistry, Radboud University Nijmegen Medical Center, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Antoine A
authors: AA
authors: Robbesom
authors: Mieke M J F
authors: MM
authors: Koenders
authors: Nicole C
authors: NC
authors: Smits
authors: Theo
authors: T
authors: Hafmans
authors: Elly M M
authors: EM
authors: Versteeg
authors: Johan
authors: J
authors: Bulten
authors: Jacques H
authors: JH
authors: Veerkamp
authors: P N Richard
authors: PN
authors: Dekhuijzen
authors: Toin H
authors: TH
authors: van Kuppevelt
mesh_terms: D000368:Aged; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D000071838:Fibrillin-1; D000071837:Fibrillins; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D054392:Adipokines
chemical_list: D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse