title: Krüppel-like zinc finger proteins in end-stage COPD lungs with and without severe alpha1-antitrypsin deficiency.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is influenced by environmental and genetic factors. An important fraction of COPD cases harbor a major genetic determinant, inherited ZZ (Glu342Lys) α1-antitrypsin deficiency (AATD). A study was undertaken to investigate gene expression patterns in end-stage COPD lungs from patients with and without AATD.
  
  
  METHODS
  Explanted lungs of end-stage ZZ AATD-related (treated and non-treated with AAT augmentation therapy) and "normal" MM COPD, and liver biopsies from patients suffering from liver cirrhosis with and without ZZ AATD were used for gene expression analysis by Affymetrix microarrays or RT-PCR.
  
  
  RESULTS
  A total of 162 genes were found to be differentially expressed (p-value ≤ 0.05 and |FC| ≥ 2) between MM and ZZ COPD patients. Of those, 134 gene sets were up-regulated and 28 were down-regulated in ZZ relative to MM lung tissue. A subgroup of genes, zinc finger protein 165, snail homolog 1 (Drosophila) (SNAI1), and Krüppel-like transcription factors (KLFs) 4 (gut), 9 and 10, perfectly segregated ZZ and MM COPD patients. The higher expression of KLF 9 and KLF10 has been verified in the replication cohort with AATD-related end-stage lung emphysema and liver cirrhosis. Furthermore, higher expression of KLF9, SNAI1 and DEFA1 was found in ZZ COPD lungs without augmentation therapy relative to MM COPD or ZZ COPD with augmentation therapy.
  
  
  CONCLUSIONS
  These results reveal the involvement of transcriptional regulators of the zinc-finger family in COPD pathogenesis and provide deeper insight into the pathophysiological mechanisms of COPD with and without AATD.
authors.affiliation: Institute of Pathology, Hannover Medical School, Hanover, Germany. koczulla@med.uni-marburg.de
authors.forename: A-Rembert
authors.initials: AR
authors.lastname: Koczulla
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
authors.forename: Thomas
authors.initials: T
authors.lastname: Wolf
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.forename: Sarah
authors.initials: S
authors.lastname: Noeske
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Claus
authors.initials: C
authors.lastname: Vogelmeier
authors.forename: Nils
authors.initials: N
authors.lastname: von Neuhoff
authors.forename: Johanna
authors.initials: J
authors.lastname: Rische
authors.forename: Sabine
authors.initials: S
authors.lastname: Wrenger
authors.forename: Heiko
authors.initials: H
authors.lastname: Golpon
authors.forename: Robert
authors.initials: R
authors.lastname: Voswinckel
authors.forename: Maurizio
authors.initials: M
authors.lastname: Luisetti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ferrarotti
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000378:metabolism*
chemical_list: D051741:Kruppel-Like Transcription Factors