TY - JOUR T1 - Cigarette smoke induced Muc5AC is regulated by CARM1 in an ex-vivo airway model JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - 4875 AU - Jie Jia AU - Oliver Eickelberg AU - Ali Önder Yildirim Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/4875.abstract N2 - Chronic obstructive pulmonary disease (COPD) is a progressive lung disease caused mostly by cigarette smoke and characterized by chronic inflammation, emphysema, airway remodeling and mucus hypersecretion. Coactivator-associated arginine methyltransferase 1 (CARM1), member of protein arginine methyltransferases (PRMTs), plays a role as co-activator, participate in multiple mechanisms of gene regulation, e.g. NF-kB pathway and CBP transcriptional activity. In this study we hypothesize that CARM1 regulates mucus production in cigarette smoke stimulated mouse airway epithelial cells.Our aim was to investigate the role of CARM1 on the Muc5AC expression in cigarette smoke exposed wild-type (wt) and CARM1 heterozygous (CARM1+/-) mouse distal airway.We observed that mouse distal airway epithelial cells, which were microdissected from mouse lung, were viable during 4 days in ex-vivo cultivation. Stimulation of isolated airway for 6h and 24h with 5%, 10%, and 20% of cigarette smoke extract (CSE) induces dose- and time-dependent Muc5AC mRNA expression and increases goblet cell metaplasia. Interestingly, CARM1+/- mouse isolated airways showed a significantly enhanced Muc5AC over-expression compared to CSE treated wt mouse.Together these results demonstrate for the first time that CARM1 contributed smoke-induced Muc5AC over-expression in distal airway epithelial cell and support the notion that CARM1 may be a potential target to treat mucus hypersecretion in chronic lung diseases. ER -