title: Cell-specific gene expression in patients with usual interstitial pneumonia.
abstract: BACKGROUND
  Usual interstitial pneumonia (UIP) is characterized by extracellular matrix deposition and the development of pulmonary fibrosis. Fibroblastic foci found in the lung are believed to represent an early stage in the evolution of this disease.
  
  
  OBJECTIVE
  To compare gene expression profiles in different components of lung tissue (fibroblastic foci, adjacent epithelium, and areas of type 2 pneumocyte hyperplasia) from patients with UIP, and contrast these profiles to distal, uninvolved (control) alveolar tissue from patients undergoing lung resection for cancer.
  
  
  METHODS
  Lung resection tissue (UIP, n = 11; controls, n = 11) was snap-frozen for subsequent laser capture microdissection, followed by mRNA extraction, linear amplification, and quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  In patients with UIP, tissue inhibitor of matrix metalloprotease-1 and matrix metalloprotease (MMP)-2 gene expression was up-regulated within the fibroblastic foci compared with the overlying epithelium (p = 0.03, p = 0.02), and to control alveoli (p = 0.001, p = 0.04), respectively. MMP-9 and MMP-7, as well as osteopontin, were up-regulated in fibroblastic foci (p = 0.01, p = 0.08, p = 0.08), the adjacent epithelium (p = 0.001, p = 0.001, p = 0.03), and the hyperplastic type 2 pneumocytes (p = 0.02, p = 0.001, p = 0.08), respectively, compared with control alveoli.
  
  
  CONCLUSIONS
  Altered gene expression of important profibrotic mediators in the different cellular lung compartments in patients with UIP likely plays an important role in pathogenesis of the deranged extracellular matrix deposition and subsequent fibrosis in this condition.
authors.affiliation: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, ON, Canada L8N 3Z5.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Kelly
authors.forename: Richard
authors.initials: R
authors.lastname: Leigh
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gilpin
authors.forename: Elaine
authors.initials: E
authors.lastname: Cheng
authors.forename: Gail E M
authors.initials: GE
authors.lastname: Martin
authors.forename: Katherine
authors.initials: K
authors.lastname: Radford
authors.forename: Gerard
authors.initials: G
authors.lastname: Cox
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D055513:Connective Tissue Growth Factor; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D017563:Lung Diseases, Interstitial / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D053495:Osteopontin; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D015291:Transforming Growth Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D053495:Osteopontin; D055513:Connective Tissue Growth Factor; D015291:Transforming Growth Factors; D020782:Matrix Metalloproteinases