PT  - JOURNAL ARTICLE
AU  - Konstantinos Samitas
AU  - Nikolaos Poulos
AU  - Eleftherios Zervas
AU  - Maria Semitekolou
AU  - Harsha Kariyawasam
AU  - Vily Panoutsakopoulou
AU  - Ying Sun
AU  - Christopher Corrigan
AU  - Georgina Xanthou
AU  - Mina Gaga
TI  - LSC 2013 abstract - Activin-A is up-regulated in severe asthma and is associated with angiogenesis
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - PP153
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/PP153.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/PP153.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - Background: Activin-A (Act-A) is a cytokine belonging to the TGF-β superfamily. Our group has shown that Act-A suppresses mouse allergic responses; however its effects on human asthma remain unknown.Objectives: Determine Act-A expression in the serum (steady-state and during exacerbation), in bronchoalveolar lavage (BALF) and bronchial tissue of healthy controls (CTRL) and asthmatics with mild-moderate (MMA) and severe asthma (SA), identify its cellular sources, examine its signaling mediators' expression and investigate possible correlations with disease severity and airway remodeling.Methods: Act-A expression was quantified in BALF (ELISA), bronchial tissue (IHC) and serum obtained from CTRL (n=41), MMA (n=48) and SA (n=26). Act-A signaling (ActRIIA, ALK4, pSMad2/3) and remodeling markers (RBM thickness, goblet cell hyperplasia, angiogenesis) were also assessed (IHC/IF/Confocal). In vitro cultures (HPMECs) and angiogenesis models (V2A kit) were used to assess the role of Act-A in angiogenesis.Results: Act-A levels were significantly increased in the serum, particularly during exacerbations, as well as in BALF and bronchial tissue of asthmatics, especially in the subepithelium of SA. T cells, neutrophils, mast cells, macrophages and endothelial cells expressed Act-A. ActRIIA, ALK4 and pSMad2/3 expression was downregulated especially in SA. Regarding remodeling, subepithelial Act-A expression correlated with tissue angiogenesis and Act-A/ALK4 were co-expressed in endothelial cells pointing to active signaling. Preliminary in vitro experiments suggest a pro-angiogenic role for Act-A.Conclusions: Our data suggest that Act-A plays a crucial role in the inflammatory and angiogenetic processes in asthma.