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Krüppel-like zinc finger proteins in end-stage COPD lungs with and without severe alpha1-antitrypsin deficiency

A-Rembert Koczulla12*, Danny Jonigk1, Thomas Wolf34, Christian Herr5, Sarah Noeske2, Walter Klepetko6, Claus Vogelmeier12, Nils von Neuhoff3, Johanna Rische1, Sabine Wrenger7, Heiko Golpon7, Robert Voswinckel8, Maurizio Luisetti9, Ilaria Ferrarotti9, Tobias Welte7 and Sabina Janciauskiene7*

Author Affiliations

1 Institute of Pathology, Hannover Medical School, Hanover, Germany

2 Department of Internal Medicine, Division of Pulmonary Diseases, Hospital of the Philipps-Universität Marburg, Baldingerstrasse 1, Marburg, D-35043, Germany

3 Institute of Molecular Pathology, Hannover Medical School, Hanover, Germany

4 Department of Theoretical Bioinformatics, German Cancer Research Center DKFZ, Heidelberg, Germany

5 Department of Internal Medicine V, Pulmonology, Allergology, Respiratory and Environmental Medicine, Saarland University Hospital, Homburg/Saar, Germany

6 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

7 Department of Respiratory Medicine, Hannover Medical School, Feodor-Lynen-Str. 23, 30625, Hannover, Germany

8 University of Giessen Lung Center, Department of Internal Medicine, University Hospital Giessen, Giessen, Germany

9 Center for Diagnosis of Inherited AAT Deficiency, Laboratory of Biochemistry and Genetics, Institute for Respiratory Disease, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

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Orphanet Journal of Rare Diseases 2012, 7:29  doi:10.1186/1750-1172-7-29

Published: 23 May 2012



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.


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.


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.


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.

Alpha 1-antitrypsin; COPD; Gene expression, Krüppel-like zinc finger proteins, Affymetrix gene chips