RT Journal Article SR Electronic T1 Serine and arginine-rich splicing factors as nuclear targets for TGF-β1 JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P4889 VO 42 IS Suppl 57 A1 Oskar Hallgren A1 Johan Malmström A1 Lars Malmström A1 Annika Andersson-Sjöland A1 Marie Wildt A1 Ellen Tufvesson A1 György Marko-Varga A1 Gunilla Westergren-Thorsson YR 2013 UL http://erj.ersjournals.com/content/42/Suppl_57/P4889.abstract AB Rationale: Transforming growth factor-β1 (TGF-β1) is a potent inducer of cell growth and differentiation and has been shown to be an important player in tissue remodeling processes. Myofibroblasts contributes to these processes by producing an excess of extracellular matrix proteins. TGF-β1 has been shown to induce myofibroblast differentiation and this process is mediated by the generation of alternatively spliced fibronectin, EDA. However the molecular mechanism is not fully understood and we therefore undertook a quantitative proteomic analysis to examine nuclear targets for TGF-β1.Methods: The expression of proteins in nuclear fractions from TGF-β1-stimulated lung fibroblasts was compared to non-stimulated cells by using mass spectrometry. Expression of proteins was verified with immunofluorescence and western blotting.Results: A total of 1733 proteins were identified by mass spectrometry and 76 were associated with mRNA splicing, including 22 proteins involved in splice site selection. TGF-β1 significantly altered the expression of several serine and arginine-rich proteins (SR-proteins) which have been suggested to be important for the generation of alternatively spliced fibronectin. By using an antibody against a phospho-epitope on SR-proteins, that recognize activated forms of the proteins, we could conclude that TGF-β1 activated a whole set of SR-proteins including SRp20, SRp30, SRp40, SRp55 and SRp75.Conclusions: The results show that TGF-β1 induces and activates proteins involved in mRNA splicing and RNA processing in human lung fibroblasts. This may have an impact on the production of alternative isoforms of matrix proteins and can therefore be an important factor in tissue remodeling.