New insights about myofibrillar myopathies: the role of metalloproteinases 2 and 9 in the pathogenesis

Authors

  • Alzira Alves de Siqueira Carvalho aDepartamento de Neurociências- Laboratório de doenças neuromusculares da FMABC, Centro Universitário FMABC, Santo André, SP, Brasil bLaboratório de Delineamento de Estudos e Escrita Científica – Centro Universitário FMABC, Santo André, Brasil cLaboratoire de Pathologie musculaire –Risler, GH Pitié-Salpêtrière, 75013 Paris, France.
  • Vinicius Gomes Silva aDepartamento de Neurociências- Laboratório de doenças neuromusculares da FMABC, Centro Universitário FMABC, Santo André, SP, Brasil
  • Alan Patricio Silva bLaboratório de Delineamento de Estudos e Escrita Científica – Centro Universitário FMABC, Santo André, Brasil
  • Roseli Corazzini aDepartamento de Neurociências- Laboratório de doenças neuromusculares da FMABC, Centro Universitário FMABC, Santo André, SP, Brasil
  • Emmanuelle Lacene cLaboratoire de Pathologie musculaire –Risler, GH Pitié-Salpêtrière, 75013 Paris, France.

DOI:

https://doi.org/10.36311/jhgd.v32.12913

Keywords:

MMP-2, MMP-9, Myofibrillar myopathy, muscle biopsy, metalloproteinase

Abstract

Backgroung: There are few reports suggesting that gene expression and activation of various matrix metalloproteinases (MMPs) are deregulated. MMP-2 and MMP-9 represent the two MMPs, which degrade type IV collagen, the component of basement membrane.

Methods: We analysed the involvement of gelatinases, MMP-2 and MMP-9, in the pathogenesis of myofibrillar myopathy (MFM). Muscle specimens from 23 patients well diagnosed with MFM, were immunostained by MMP-2 and MMP-9. We analysed qualitatively the immunoexpression in three compartments: subsarcolemmal (SSC), intracytoplasmic (ICC) and perinuclear (PNC).

Results: 95,7% and 100% samples showed MMP-2 and MMP-9 upregulation ICC, respectively. PNC showed MMP-2 (82,6%) and MMP-9 (8,7%) regulation (p<0.001). SSC and ICC did not present statistical significance. There was no correlation between mutated gene and immunohistochemical pattern distribution.

Discussion: Our results suggest that MMP-2 and/or MMP-9 could participate in the pathomechanism of MFM, causing damage of sarcomere and deposition of protein aggregates.

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References

Wang W, Schulze CJ, Suarez-Pinzon WL, Dyck JR, SawickiG, Schulz R. Intracellular action of matrix metalloproteinase-2 accounts for acute myocardial ischemia and reperfusion injury. Circulation. 2002;106: 1543–1549.

Sung MM, Schulz CG, Wang W, Sawicki G, Bautista-Lopez NL, Schulz R. Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. J Mol Cell Cardiol. 2007; 43:429-36

DeCoux A, Lindsey ML, Villarreal F, Garcia RA, Schulz R. Myocardial matrix metalloproteinase-2: inside out and upside down. J Mol Cell Cardiol. 2014; 77:64-72

Schulz R. Intracellular Target of Matrix Metalloproteinase-2 in Cardiac Disease: Rationale and Therapeutic Approaches. Annu Rev Pharmacol Toxicol. 2007;47: 211-42

Ogura Y, Tajrishi MM, Sato S, Hindi SM, Kumar A. Therapeutic potential of matrix metalloproteinase in Duchenne muscular dystrophy. Front Cell Dev Biol. 2014; 2: 1-11.

Fukushima K, Nakamura A, Ueda H, Yuasa K, Yoshida K, Takeda S et al. Activation and localization of matrix metalloproteinase-2 and -9 in the skeletal muscle of the muscular dystrophy dog (CXMDJ). BMC Musculoskelet Disord. 2007 Jun 28; 8:54.

Choi YC, Dalakas MC. Expression of matrix metalloproteinases in the muscle of patients with inflammatory myopathies. Neurology 2000 Jan 11; 54(1): 65-71

Schoser BGH, Blottner D, Stuerenburg HJ. Matrix metalloproteinases in inflammatory myopathies: enhanced immunoreactivity near atrophic myofibers. Acta Neurol Scand 2002: 105: 309-13

Béhin A, Salort-Campana E, Wahbi K, Richard P, Carlier RY, Carlier P et al. Myofibrillar myopathies: State of the art, present and future challenges. Rev Neurol (Paris). 2015 Oct; 171(10): 715-29

Ferrer I; Olivé M. Molecular pathology of myofibrillar myopathies. Expert Rev Mol Med. 2008; 10 Sep 3;10: e25. doi: 10.1017/S1462399408000793.

Rosner B. Fundamentals of Biostatistics. Boston. PWS Publishers. Second edition. 1986. 584pp.

Acharyya S, Villalta SA, Bakkar N, Bupha-Intr T, Janssen PM, Carathers M et al. Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J. Clin. Invest.2007; 117, 889–901

Carlson BM, Faulkner JA. The regeneration of skeletal muscle fibers following injury: a review. Med Sci Sports Exerc. 1983; 15(3): 187-98.

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Published

2022-01-31

Issue

Vol. 32 No. 1 (2022)

Section

ORIGINAL ARTICLES

License

Copyright (c) 2022 Carvalho AAS, Silva VG, Silva AP, Corazzini R, Lacene E

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.