PT  - JOURNAL ARTICLE
AU  - Paulina Rolewska
AU  - Samiya Al-Robaiy
AU  - Andreas Simm
AU  - Rolf-Edgar Silber
AU  - Babett Bartling
TI  - Ageing lung shows reduced expression and activation of the <em>cyclic AMP response element binding protein</em>
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P3404
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P3404.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P3404.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - Background: Lung ageing is associated with morphological and, therefore, physiological changes. While much attention has been paid to changes of the extracellular matrix, less is known about the effect of ageing on intracellular compounds including transcription factors. As the transcription factor cyclic AMP response element binding protein (CREB) is involved in various cellular mechanisms, including glucose metabolism and growth factor-dependent cell survival, our study aimed at effect of lung ageing on CREB. Methods: Lung tissues of young, adult and old mice were studied by PCR, immunoblot and immunohistochemisty. Moreover, we studied pre-senescent and senescent primary human lung fibroblasts, and the effect of known age-related factors. Results: Lung tissue was characterized by an age-dependent reduction of activated (phosphorylated) and total CREB protein, whereas ageing did not influence the mRNA level of CREB. The mRNA of the phosphoenolpyruvate carboxykinase 1, which is a target of active CREB, was also reduced in old lung tissue. In this regard, the protein but not mRNA level of CREB was lower in senescent than pre-senescent lung fibroblasts. Down-regulation of CREB by siRNA transfection caused a lower maximal population doubling and higher cell death of human fibroblasts in vitro. Among several age-related factors we identified the increased non-enzymatic modification of the extracellular matrix with advanced glycation end-products as one reason for the reduced level of CREB protein in old lung tissues. Conclusion: The reduction of active CREB might contribute to morphological and physiological changes in the ageing lung by a lower transcription of CREB target genes.