@article {SarkerP661, author = {Rim S.J. Sarker and Alexander Bohla and Gerrit John and Katrin Kohse and Oana Veronica Amarie and MarK T. Bedford and Oliver Eickelberg and Ali {\"O}nder Yildirim}, title = {Involvement of coactivator associated arginine methyltransferase 1 (CARM1) in development of elastase-induced progressive emphysema}, volume = {42}, number = {Suppl 57}, elocation-id = {P661}, year = {2013}, publisher = {European Respiratory Society}, abstract = {Chronic obstructive pulmonary disease comprises chronic bronchitis and emphysema. Emphysema is characterized by destruction of alveolar walls leading to enlarged air spaces and reduced surface area. CARM1-an arginine methyltransferase and a coactivator to regulate transcription, translation and DNA repair is found important for regulating proliferation and differentiation of pulmonary epithelial cells (O{\textquoteright}Brien, 2010). We wanted to investigate its role in emphysema development and progression.Porcine pancreatic elastase (PPE) was applied to C57BL/6 mice. Lung function, histology and gene expression were analyzed on day 2, 28, 56, and 161. CARM1+/- mice were analyzed on day 28. LA-4 alveolar cells were treated with CARM1 siRNA. Proliferative, apoptotic characteristics were measured by gene expression or wound healing assays.PPE-treated wild-type mice showed significant increased forced residual capacity, total lung capacity, dynamic lung compliance and decreased Tiffeneau index correlated to increased mean linear chord length (Lm) in a time dependent manner. qRT-PCR showed decreased proliferation (Cyclin D1) and increased apoptosis marker (Bax) in lung. CARM1 expression was significantly diminished. PPE-treated CARM1+/- mice displayed impaired lung function and enhanced Lm compared to wild type. Furthermore, silencing of CARM1 by siRNA in LA-4 cells led to reduced migration and proliferation.PPE treated wild type mice developed progressive emphysema and impaired lung function during 161 days of analysis. CARM1+/- mice showed to be more susceptible to emphysema progression. Pharmacological implication of CARM1 could be a prospectus therapy for COPD.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/42/Suppl_57/P661}, eprint = {https://erj.ersjournals.com/content/42/Suppl_57/P661.full.pdf}, journal = {European Respiratory Journal} }