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Alternative splicing factor ASF/SF2 is down regulated in inflamed muscle
  1. Z Xiong1,2,
  2. A Shaibani3,4,
  3. Y-P Li3,
  4. Y Yan2,
  5. S Zhang1,2,
  6. Y Yang2,
  7. F Yang1,2,
  8. H Wang1,3,5,
  9. X-F Yang1,2,3,6
  1. 1Laboratory of Immunopathology, Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
  2. 2Laboratory of Immunopathology, Baylor College of Medicine, Houston, Texas, USA
  3. 3Department of Medicine, Baylor College of Medicine
  4. 4Nerve & Muscle Center of Texas, St Luke’s Episcopal Hospital, Houston
  5. 5Biology of Inflammation Center, Section of Atherosclerosis and Lipoprotein Research, Baylor College of Medicine
  6. 6Department of Immunology, Baylor College of Medicine
  1. Correspondence to:
 X-F Yang
 Department of Pharmacology, Temple University School of Medicine, 3420 N Broad Street, MRB Room 300, Philadelphia, PA 19140, USA; franklinxf_yang{at}yahoo.com

Abstract

Background: In our recent studies, alternative splicing has been shown to have a major role in inflammation and autoimmune muscle diseases.

Aim: To examine the novel hypothesis that the expression of an essential alternative splicing factor, alternative splicing factor 2 (ASF/SF2), is modulated in muscle inflammation.

Methods: ASF/SF2 expression in muscle biopsy samples from eight patients with inflammatory myopathy and six non-myositic controls was determined by using western blot with anti-ASF/SF2 antibodies. To further elucidate the mechanism of reduced ASF/SF2 expression in inflamed muscle, differentiated C2C12 myotubes were stimulated with proinflammatory cytokine tumour necrosis factor α (TNFα), followed by western blot analysis of ASF/SF2 expression.

Results: ASF/SF2 expression in the muscle biopsy samples from patients with inflammatory myopathy was found to be lower (mean of relative densitometric units 41.1 (2SD 20.7)) than that of the non-myositic controls (mean of relative densitometric units 76.7 (39.6); p<0.05). In addition to this, ASF/SF2 expression was seen to be significantly down regulated (sevenfold) in C2C12 myotubes compared with expression variations in the β-actin control (0.62-fold; mean 1.22 (0.40); p<0.05).

Conclusion: Collectively, it is shown, for the first time, that alternative splicing factor ASF/SF2 is down regulated in autoimmune inflammatory myositis—potentially via a TNFα-mediated pathway. The development of (1) novel autoantigen isoform microarrays for disease diagnosis and prognosis; (2) novel autoantigen-tolerising treatments for autoimmune diseases; and (3) novel splicing-redirection treatments can be facilitated by the ongoing study of alternative splicing of autoantigen transcripts.

  • ASF/SF2, alternative splicing factor 2
  • mRNA, messenger RNA
  • PM, polymyositis
  • SR protein, serine/arginine-rich protein
  • TNFα, tumour necrosis factor α

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Footnotes

  • Published Online First 30 March 2006

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