Splicosomal and serine and arginine-rich splicing factors as targets for TGF-beta.
|Nr||31 (Research article)|
|Authors||Hallgren, Oskar; Malmström, Johan; Malmström, Lars; Andersson-Sjöland, Annika; Wildt, Marie; Tufvesson, Ellen; Juhasz, Peer; Marko-Varga, Gyorgy; Westergren-Thorsson, Gunilla|
|Title||Splicosomal and serine and arginine-rich splicing factors as targets for TGF-beta.|
|Journal||Fibrogenesis Tissue Repair (2012) 5 6|
|Citations||15 citations (journal impact: 2.97)|
|Abstract||ABSTRACT BACKGROUND Transforming growth factor-beta1 TGF-beta1 is a potent regulator of cell growth and differentiation. TGF-beta1 has been shown to be a key player in tissue remodeling processes in a number of disease states by inducing expression of extracellular matrix proteins. In this study a quantitative proteomic analysis was undertaken to investigate if TGF-beta1 contributes to tissue remodeling by mediating mRNA splicing and production of alternative isoforms of proteins. MethodologyPrincipal findings The expression of proteins involved in mRNA splicing from TGF-beta1-stimulated lung fibroblasts was compared to non-stimulated cells by employing isotope coded affinity tag ICATTM reagent labeling and tandem mass spectrometry. A total of 1733 proteins were identified and quantified with a relative standard deviation of 11 8 from enriched nuclear fractions. Seventy-six of these proteins were associated with mRNA splicing including 22 proteins involved in splice site selection. In addition TGF-beta1 was observed to alter the relative expression of splicing proteins that may be important for alternative splicing of fibronectin. Specifically TGF-beta1 significantly induced expression of SRp20 and reduced the expression of SRp30C which has been suggested to be a prerequisite for generation of alternatively spliced fibronectin. The induction of SRp20 was further confirmed by western blot and immunofluorescence. CONCLUSIONS The results show that TGF-beta1 induces the expression of 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 and disease progression.|