PMID- 22621770
OWN - NLM
STAT- MEDLINE
DCOM- 20130410
LR  - 20211021
IS  - 1750-1172 (Electronic)
IS  - 1750-1172 (Linking)
VI  - 7
DP  - 2012 May 23
TI  - Kruppel-like zinc finger proteins in end-stage COPD lungs with and without severe 
      alpha1-antitrypsin deficiency.
PG  - 29
LID - 10.1186/1750-1172-7-29 [doi]
AB  - 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) alpha1-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 Kruppel-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.
FAU - Koczulla, A-Rembert
AU  - Koczulla AR
AD  - Institute of Pathology, Hannover Medical School, Hanover, Germany. 
      koczulla@med.uni-marburg.de
FAU - Jonigk, Danny
AU  - Jonigk D
FAU - Wolf, Thomas
AU  - Wolf T
FAU - Herr, Christian
AU  - Herr C
FAU - Noeske, Sarah
AU  - Noeske S
FAU - Klepetko, Walter
AU  - Klepetko W
FAU - Vogelmeier, Claus
AU  - Vogelmeier C
FAU - von Neuhoff, Nils
AU  - von Neuhoff N
FAU - Rische, Johanna
AU  - Rische J
FAU - Wrenger, Sabine
AU  - Wrenger S
FAU - Golpon, Heiko
AU  - Golpon H
FAU - Voswinckel, Robert
AU  - Voswinckel R
FAU - Luisetti, Maurizio
AU  - Luisetti M
FAU - Ferrarotti, Ilaria
AU  - Ferrarotti I
FAU - Welte, Tobias
AU  - Welte T
FAU - Janciauskiene, Sabina
AU  - Janciauskiene S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120523
PL  - England
TA  - Orphanet J Rare Dis
JT  - Orphanet journal of rare diseases
JID - 101266602
RN  - 0 (Kruppel-Like Transcription Factors)
SB  - IM
MH  - Case-Control Studies
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - Kruppel-Like Transcription Factors/genetics/*metabolism
MH  - Lung/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Pulmonary Disease, Chronic Obstructive/complications/genetics/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - alpha 1-Antitrypsin Deficiency/complications/*metabolism
PMC - PMC3517304
EDAT- 2012/05/25 06:00
MHDA- 2013/04/11 06:00
PMCR- 2012/05/23
CRDT- 2012/05/25 06:00
PHST- 2011/11/24 00:00 [received]
PHST- 2012/05/08 00:00 [accepted]
PHST- 2012/05/25 06:00 [entrez]
PHST- 2012/05/25 06:00 [pubmed]
PHST- 2013/04/11 06:00 [medline]
PHST- 2012/05/23 00:00 [pmc-release]
AID - 1750-1172-7-29 [pii]
AID - 10.1186/1750-1172-7-29 [doi]
PST - epublish
SO  - Orphanet J Rare Dis. 2012 May 23;7:29. doi: 10.1186/1750-1172-7-29.