TY - JOUR T1 - Implication of microRNA-148b in chronic obstructive lung disease of βENaC-overexpressing mice JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - 1506 AU - Raman Agrawal AU - Mirco Castoldi AU - Sandro Altamura AU - Michael Meister AU - Thomas Muley AU - Catherine Greene AU - Martina Muckenthaler AU - Marcus Mall Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/1506.abstract N2 - MicroRNAs are involved in diverse biological and pathological processes. Here, we studied the potential role of miRNAs in the in vivo pathogenesis of chronic obstructive pulmonary disease (COPD) using βENaC-overexpressing (βENaC-Tg) mouse model. We performed miRNA array analysis in lung tissue of βENaC-Tg and wild-type (WT) mice. Differentially expressed miRNAs were validated by qRT-PCR and their functional importance was determined by bioinformatics analysis and in luciferase reporter assays. Tissue specific localization was performed by in situ hybridization using locked nucleic acid-modified DNA probe. Direct functional studies were performed by knockdown of miRNA expression in the lungs of βENaC-Tg mice using antagomirs. The effects of knockdown were studied by lung histology, pulmonary function testing using flexiVent system and analysis of inflammatory cells in bronchoalveolar lavage. We demonstrate that miR-148b is upregulated in the lungs of βENaC-Tg mice and predominantly localized in the conducting airways. Luciferase reporter assay in Hela cells suggests Mig-6 (mitogen inducible gene-6), a protein previously shown in normal lung development, as a potential target of miR-148b. Knockdown of miR-148b in the lung of βENaC-Tg mice results in reduced emphysema and decreased numbers of neutrophils compared to WT mice. Moreover, we observed upregulation of miR-148b in bronchial brushing of cystic fibrosis and COPD lung tissue from human. Taken together, these results indicate that dysregulation of miR-148b expression may play an important role in the pathogenesis of COPD and may serve as a novel therapeutic target.Supported by BMBF (82DZL00401). ER -