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Increased mRNA expression of tissue inhibitors of metalloproteinase-1 and -2 in Duchenne muscular dystrophy

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Abstract

In dystrophinopathies, disease severity is generally related to the extent of muscle fibrosis. To determine whether a decrease in matrix degradation contributes to the severe fibrosis seen in Duchenne muscular dystrophy (DMD), we quantified RNA transcript numbers for the fibrolytic matrix metalloproteinases (MMP)-1 and −2 and their natural tissue inhibitors (TIMP)-1 and −2 in DMD muscle as well as in pathological and normal controls. In addition, we investigated gelatinase (MMP-2) enzyme activity by zymography. We found an up-regulation of TIMP-1, TIMP-2 and MMP-2 RNA in DMD muscle. Zymography revealed an increase in MMP-2 activity in DMD muscle homogenates, which was absent in pathological and normal controls. Therefore, besides enhanced fibrogenesis, a disturbance of matrix degradation may play a significant role in muscle fibrosis in DMD. TIMP-1 should be investigated further as a promising target for pharmacological intervention to prevent muscle fibrosis in DMD.

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Acknowledgements

The authors gratefully acknowledge the financial support of the Sanitätsrat Dr. Emil Alexander Huebner und Gemahlin-Stiftung (TS 114/61/96) and the Deutsche Gesellschaft für Muskelkranke (DGM).

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Authors and Affiliations

  1. Department of Neuropediatrics, Charité, University Medical Center Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Arpad von Moers, Angelika Zwirner, Anke Reinhold, Olaf Brückmann & Markus Schuelke

  2. Institute of Neuropathology, Charité, University Medical Center Berlin, Berlin, Germany

    Frank van Landeghem & Gisela Stoltenburg-Didinger

  3. Department of Gastroenterology and Hepatology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany

    Detlef Schuppan

  4. Institute of Pathology, University Hospital Münster, Münster, Germany

    Herrman Herbst

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  1. Arpad von Moers
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  2. Angelika Zwirner
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Correspondence to Arpad von Moers.

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von Moers, A., Zwirner, A., Reinhold, A. et al. Increased mRNA expression of tissue inhibitors of metalloproteinase-1 and -2 in Duchenne muscular dystrophy. Acta Neuropathol 109, 285–293 (2005). https://doi.org/10.1007/s00401-004-0941-0

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  • DOI: https://doi.org/10.1007/s00401-004-0941-0

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