Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle

Aurelia Defour, Sushma Medikayala, Jack H Van der Meulen, Marshall W Hogarth, Nicholas Holdreith, Apostolos Malatras, William Duddy, Jessica Boehler, Kanneboyina Nagaraju, Jyoti K Jaiswal

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Abstract

Repair of skeletal muscle after sarcolemmal damage involves dysferlin and dysferlin-interacting proteins such as annexins. Mice and patient lacking dysferlin exhibit chronic muscle inflammation and adipogenic replacement of the myofibers. Here, we show that similar to dysferlin, lack of annexin A2 (AnxA2) also results in poor myofiber repair and progressive muscle weakening with age. By longitudinal analysis of AnxA2-deficient muscle we find that poor myofiber repair due to the lack of AnxA2 does not result in chronic inflammation or adipogenic replacement of the myofibers. Further, deletion of AnxA2 in dysferlin deficient mice reduced muscle inflammation, adipogenic replacement of myofibers, and improved muscle function. These results identify multiple roles of AnxA2 in muscle repair, which includes facilitating myofiber repair, chronic muscle inflammation and adipogenic replacement of dysferlinopathic muscle. It also identifies inhibition of AnxA2-mediated inflammation as a novel therapeutic avenue for treating muscle loss in dysferlinopathy.
Original languageEnglish
Pages (from-to)1979-1991
JournalHuman Molecular Genetics
Volume26
Issue number11
Early online date21 Feb 2017
DOIs
Publication statusE-pub ahead of print - 21 Feb 2017

Keywords

  • Dysferlinopathy
  • Annexin A2
  • LGMD-2B
  • Limb Girdle Muscular Dystrophy type 2B

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    Defour, A., Medikayala, S., Van der Meulen, J. H., Hogarth, M. W., Holdreith, N., Malatras, A., Duddy, W., Boehler, J., Nagaraju, K., & Jaiswal, J. K. (2017). Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle. Human Molecular Genetics, 26(11), 1979-1991. https://doi.org/10.1093/hmg/ddx065