Comparative gene expression profiling of post-natal and post-pneumonectomy lung growth.
Although increasing numbers of patients suffer from chronic destructive lung diseases, there are no effective therapeutic options apart from transplantation. Understanding the mechanisms of physiological and regenerative alveolar septation is prerequisite for the development of regenerative therapies for the lung. We compared lung gene expression in the phase of induction of post-natal and post-pneumonectomy alveolarisation to identify regulatory genes involved in both processes. We performed genome-wide microarray screenings of newborn and pneumonectomised mouse lungs 1 and 3 days after birth or surgery. Selected candidates were validated by real-time PCR, Western blot and in situ hybridisation. We found 58 genes to be regulated in both models with 40 candidates being changed likewise. Many of these genes participated in growth and differentiation processes. Additionally, immune system, structural molecules, respiratory chain, signal transduction and metabolism were involved. Some candidates were not yet linked to specific functions. The highest regulatory concordance was observed for various isoforms of (pro-)collagen molecules, elastin and the elastin-associated protein fibrillin1 being corporately upregulated. Our findings do not definitively support a common regulating mechanism for induction of post-natal and adult alveolarisation, but some candidates in the intersection of both models are promising for further investigations.
Wolff
J-C
JC
Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany. Jens-Christian.Wolff@mpi-bn.mpg.de
Wilhelm
J
J
Fink
L
L
Seeger
W
W
Voswinckel
R
R
D000209:Acute-Phase Proteins / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D000071838:Fibrillin-1; D000071837:Fibrillins; D020869:Gene Expression Profiling; D016762:Genes, fos; D006801:Humans; D017403:In Situ Hybridization; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics; D008115:Liver Regeneration / Q000235:genetics*; D008168:Lung / Q000254:growth & development*; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics; D011013:Pneumonectomy; D016133:Polymerase Chain Reaction; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D054392:Adipokines
D000209:Acute-Phase Proteins; D004549:Elastin; D000071838:Fibrillin-1; D000071837:Fibrillins; D000071068:Lipocalin-2; D054834:Lipocalins; D008840:Microfilament Proteins; D015513:Oncogene Proteins; D011347:Procollagen; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse; C071332:Lcn2 protein, mouse