Extracellular matrix composition is modified by beta(2)-agonists through cAMP in COPD

Lambers, Chistopher and Qi, Ying and Eleni, Papakonstantinou and Costa, Luigi and Zhong, Jun and Tamm, Michael and Block, Lutz Henning and Roth, Michael. (2014) Extracellular matrix composition is modified by beta(2)-agonists through cAMP in COPD. Biochemical Pharmacology, 91 (3). pp. 400-408.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/62438/

Downloads: Statistics Overview


Long acting beta(2)-agonists (LABA) have been reported to modify the extracellular matrix (ECM) composition in the airway wall. Based on our earlier studies we here investigated the mechanism underlying the control of ECM modification by LABA in primary human airway smooth muscle cells. Cells were treated with formoterol or salmeterol (30 min) before TGF-beta(1) stimulation (2-3 days) Using RT-PCT, immuno-blotting and ELISA the de novo synthesis and deposition of collagen type-I, -III, -IV and fibronectin were determined. Matrix metalloproteinases (MMP)-2 and -9 were analyzed by zymography. Both LABA activated cAMP and its corresponding transcription factor CREB within 60 min and thus partly reduced TGF-beta(1)-induced gene transcription of collagen type-I, -III, fibronectin and connective tissue growth factor (CTGF). The inhibitory effect of both LABA on collagen type-I and -III deposition involved a cAMP dependent mechanism, while the inhibitory effect of the two drugs on TGF-beta1-induced fibronectin deposition and on CTGF secretion was independent of cAMP. Interestingly, none of the two LABA reduced CTGF-induced synthesis of collagen type-I or type-III deposition. In addition, none of the two LABA modified collagen type-IV deposition or the expression and activity of MMP-2 or MMP-9. Our results show that LABA can prevent de novo deposition of specific ECM components through cAMP dependent and independent signaling. However, they do not reduce all ECM components by the same mechanism and they do not reduce existing collagen deposits. This might explain some of the controversial reports on the anti-remodeling effect of LABA in chronic inflammatory lung diseases.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Pulmonary Cell Research (Roth/Tamm)
UniBasel Contributors:Roth-Chiarello, Michael and Tamm, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:04 Aug 2020 12:00
Deposited On:04 Aug 2020 12:00

Repository Staff Only: item control page