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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.
LanguageEnglish
Pages1979-1991
JournalHuman Molecular Genetics
Volume26
Issue number11
Early online date21 Feb 2017
DOIs
Publication statusE-pub ahead of print - 21 Feb 2017

Fingerprint

Annexins
Annexin A2
Inflammation
Muscles
Skeletal Muscle

Keywords

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

Cite this

Defour, A., Medikayala, S., Van der Meulen, J. H., Hogarth, M. W., Holdreith, N., Malatras, A., ... 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
Defour, Aurelia ; Medikayala, Sushma ; Van der Meulen, Jack H ; Hogarth, Marshall W ; Holdreith, Nicholas ; Malatras, Apostolos ; Duddy, William ; Boehler, Jessica ; Nagaraju, Kanneboyina ; Jaiswal, Jyoti K. / Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle. In: Human Molecular Genetics. 2017 ; Vol. 26, No. 11. pp. 1979-1991.
@article{fdeca7d49d3c4e7e95aafb05b642e68e,
title = "Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle",
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.",
keywords = "Dysferlinopathy, Annexin A2, LGMD-2B, Limb Girdle Muscular Dystrophy type 2B",
author = "Aurelia Defour and Sushma Medikayala and {Van der Meulen}, {Jack H} and Hogarth, {Marshall W} and Nicholas Holdreith and Apostolos Malatras and William Duddy and Jessica Boehler and Kanneboyina Nagaraju and Jaiswal, {Jyoti K}",
year = "2017",
month = "2",
day = "21",
doi = "10.1093/hmg/ddx065",
language = "English",
volume = "26",
pages = "1979--1991",
journal = "Human Molecular Genetics",
issn = "0964-6906",
number = "11",

}

Defour, A, Medikayala, S, Van der Meulen, JH, Hogarth, MW, Holdreith, N, Malatras, A, Duddy, W, Boehler, J, Nagaraju, K & Jaiswal, JK 2017, 'Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle', Human Molecular Genetics, vol. 26, no. 11, pp. 1979-1991. https://doi.org/10.1093/hmg/ddx065

Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle. / Defour, Aurelia; Medikayala, Sushma; Van der Meulen, Jack H; Hogarth, Marshall W; Holdreith, Nicholas; Malatras, Apostolos; Duddy, William; Boehler, Jessica; Nagaraju, Kanneboyina; Jaiswal, Jyoti K.

In: Human Molecular Genetics, Vol. 26, No. 11, 21.02.2017, p. 1979-1991.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle

AU - Defour, Aurelia

AU - Medikayala, Sushma

AU - Van der Meulen, Jack H

AU - Hogarth, Marshall W

AU - Holdreith, Nicholas

AU - Malatras, Apostolos

AU - Duddy, William

AU - Boehler, Jessica

AU - Nagaraju, Kanneboyina

AU - Jaiswal, Jyoti K

PY - 2017/2/21

Y1 - 2017/2/21

N2 - 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.

AB - 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.

KW - Dysferlinopathy

KW - Annexin A2

KW - LGMD-2B

KW - Limb Girdle Muscular Dystrophy type 2B

U2 - 10.1093/hmg/ddx065

DO - 10.1093/hmg/ddx065

M3 - Article

VL - 26

SP - 1979

EP - 1991

JO - Human Molecular Genetics

T2 - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 11

ER -

Defour A, Medikayala S, Van der Meulen JH, Hogarth MW, Holdreith N, Malatras A et al. Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle. Human Molecular Genetics. 2017 Feb 21;26(11):1979-1991. https://doi.org/10.1093/hmg/ddx065