title: Reduced phosphorylation of the TGF-Beta signal transducer Smad2 in emphysematous human lung.
abstract: Chronic obstructive pulmonary disease (COPD) is characterized by inflammatory immune response, emphysematous destruction of alveolar structures and obstruction in the small conducting airways. Transforming growth factor (TGF)-beta is involved in the maintenance of normal lung tissue homeostasis as a regulator of extracellular proteolysis, tissue repair and inflammatory functions. This study was undertaken to characterize TGF-beta signaling in pathologically distinct areas of COPD lungs. Using Smad2 phosporylation (P-Smad2) as an indicator of TGF-beta signaling activity we analyzed COPD patient tissues and controls by immunohistochemistry. Emphysematous lung showed significantly reduced P-Smad2 immunoreactivity both in the alveolar and bronchiolar epithelium, which is evidence of reduced TGF-beta signaling activity. On the contrary, in the thickened peribronchial areas there was an increase in the amount of P-Smad2 positive cells. Isolated COPD lung fibroblasts also displayed increased TGF-beta signaling and target gene expression suggesting that the fibroblasts are characteristic to the small airway disease phenotype. Our results indicate that TGF-beta signaling activity is differentially regulated in distinct areas of COPD lung and likely contributes to both emphysematous development and small airway obstruction.
authors.affiliation: Department of Medicine, Pulmonary Division, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. outi.lepparanta@helsinki.fi
authors.forename: Outi
authors.initials: O
authors.lastname: Leppäranta
authors.forename: Marjukka
authors.initials: M
authors.lastname: Myllärniemi
authors.forename: Kaisa
authors.initials: K
authors.lastname: Salmenkivi
authors.forename: Vuokko L
authors.initials: VL
authors.lastname: Kinnula
authors.forename: Jorma
authors.initials: J
authors.lastname: Keski-Oja
authors.forename: Katri
authors.initials: K
authors.lastname: Koli
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051899:Smad2 Protein / Q000378:metabolism*; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology
chemical_list: C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta