TY - JOUR T1 - Identification of novel proteins involved in β-catenin dependent alveolar epithelial trans-differentiation JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3911 AU - Kathrin Mutze AU - Jadranka Milosevic AU - Julia Kipp AU - Oliver Eickelberg AU - Melanie Königshoff Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3911.abstract N2 - Objective: The alveolar epithelium consists of alveolar epithelial type 1 (AT1) and type 2 (AT2) cells and represents a major site of tissue destruction in idiopathic pulmonary fibrosis. Adult AT2 cells can self-renew and exert progenitor function for AT1 cells upon alveolar injury. Cell differentiation pathways enabling this plasticity, however, are poorly understood. Here we use primary cultures of murine AT2 cells as model system to identify novel proteins involved in AT2 to AT1 transdifferentiation.Methods: Changes in protein expression of cultured AT2 cells (day 1-5) were analyzed using 2D gel electrophoresis/mass spectrometry and confirmed by qRT-PCR/immunoblotting. Primary AT2 cells form experimental fibrosis were evaluated regarding expression of genes regulated by transdifferentiation.Results: Beside others, we found enolase 1 (ENO1) to be upregulated in transdifferentiating AT2 cells, whereas carbonyl reductase 2 (CBR2) was decreased. This was accompanied by reduction in AT2 cell derived surfactant protein C (SPC) expression and increased AT1 cell T1a expression. Inhibition of Wnt/β-catenin signaling, which is upregulated during transdifferentiation and in fibrosis, resulted in decreased expression of ENO1 and T1a and stabilization of CBR2. In vivo, CBR2 and SPC expression was decreased, whereas ENO1 and T1a expression was increased in freshly isolated fibrotic AT2 cells.Conclusion: Proteomic analysis revealed novel proteins differentially expressed in trans-differentiating AT2 cells. Interestingly, newly identified proteins were regulated by β-catenin in vitro and in experimental fibrosis in vivo, suggesting a role in epithelial repair processes upon lung injury. ER -