Reduced phosphorylation of the TGF-Beta signal transducer Smad2 in emphysematous human lung.
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.
Leppäranta
Outi
O
Department of Medicine, Pulmonary Division, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. outi.lepparanta@helsinki.fi
Myllärniemi
Marjukka
M
Salmenkivi
Kaisa
K
Kinnula
Vuokko L
VL
Keski-Oja
Jorma
J
Koli
Katri
K
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
C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta