title: Splicosomal and serine and arginine-rich splicing factors as targets for TGF-β.
abstract: BACKGROUND
  Transforming growth factor-β1 (TGF-β1) is a potent regulator of cell growth and differentiation. TGF-β1 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-β1 contributes to tissue remodeling by mediating mRNA splicing and production of alternative isoforms of proteins.
  
  
  RESULTS
  The expression of proteins involved in mRNA splicing from TGF-β1-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-β1 was observed to alter the relative expression of splicing proteins that may be important for alternative splicing of fibronectin. Specifically, TGF-β1 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-β1 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.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden. oskar.hallgren@med.lu.se.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hallgren
authors.forename: Johan
authors.initials: J
authors.lastname: Malmström
authors.forename: Lars
authors.initials: L
authors.lastname: Malmström
authors.forename: Annika
authors.initials: A
authors.lastname: Andersson-Sjöland
authors.forename: Marie
authors.initials: M
authors.lastname: Wildt
authors.forename: Ellen
authors.initials: E
authors.lastname: Tufvesson
authors.forename: Peter
authors.initials: P
authors.lastname: Juhasz
authors.forename: György
authors.initials: G
authors.lastname: Marko-Varga
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson