von Moers Arpad, Zwirner Angelika, Reinhold Anke, Brückmann Olaf, van Landeghem Frank, Stoltenburg-Didinger Gisela, Schuppan Detlef, Herbst Herrman, Schuelke Markus
Department of Neuropediatrics, Charité, University Medical Center Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Acta Neuropathol. 2005 Mar;109(3):285-93. doi: 10.1007/s00401-004-0941-0. Epub 2004 Dec 23.
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.
在肌营养不良症中，疾病严重程度通常与肌肉纤维化程度相关。为了确定基质降解减少是否导致杜氏肌营养不良症（DMD）中出现的严重纤维化，我们对DMD肌肉以及病理和正常对照中的纤溶基质金属蛋白酶（MMP）-1和-2及其天然组织抑制剂（TIMP）-1和-2的RNA转录本数量进行了定量。此外，我们通过酶谱法研究了明胶酶（MMP-2）的酶活性。我们发现DMD肌肉中TIMP-1、TIMP-2和MMP-2 RNA上调。酶谱分析显示DMD肌肉匀浆中MMP-2活性增加，而病理和正常对照中不存在这种情况。因此，除了增强的纤维化形成外，基质降解紊乱可能在DMD的肌肉纤维化中起重要作用。TIMP-1作为预防DMD肌肉纤维化的有前景的药物干预靶点应进一步研究。
