Kunert-Keil Christiane, Gredes Tomasz, Lucke Silke, Morgenstern Sven, Mielczarek Agnieszka, Sporniak-Tutak Katarzyna, Gedrange Tomasz, Spassov Alexander
Department of Orthodontics, Preventive and Pediatric Dentistry, Ernst Moritz Arndt University of Greifswald, Germany.
Folia Histochem Cytobiol. 2011;49(2):291-8. doi: 10.5603/fhc.2011.0041.
Duchenne muscular dystrophy (DMD) and murine X-linked muscular dystrophy (mdx), its murine model, are characterized by muscle damage and muscle weakness associated with inflammation and new vessel formation. Caveolins, dystrophin-associated proteins, are involved in the pathogenesis of DMD, because increased numbers of caveolae are found in DMD and mdx hindlimb muscles. Caveolae influence angiogenesis due to their content of vascular endothelial growth factor (VEGF) receptors. Orofacial muscles in mdx mice undergo muscle necrosis followed by muscle regeneration. To ascertain the role of caveolins and VEGF in the pathogenesis of dystrophic masticatory muscles, we examined the expression of caveolin-1 (cav-1), caveolin-3 (cav-3) and VEGF in control and mdx mice. In mdx masticatory muscles, no changes in transcript and protein levels of VEGF were found, whereas cav-1 and cav-3 expression was increased. Using immunohistochemistry, a strong sarcolemmal staining of caveolin-3 in regenerated muscle fibers was found. Furthermore, immunohistochemistry with the caveolin-1 antibody showed an increase in the amount of blood vessels in areas with regenerating muscle fibers. Dystrophic masticatory muscles showed changes comparable to those of hindlimb muscles in the expression of cav-1 and cav-3. The angiogenesis seems to be unaffected in the jaw muscles of mdx mice. We speculate that the increased caveolin expression could cause extensive and efficient muscle regeneration.
杜兴氏肌营养不良症（DMD）及其小鼠模型——小鼠X连锁肌营养不良症（mdx）的特征是与炎症和新血管形成相关的肌肉损伤和肌肉无力。小窝蛋白是与肌营养不良蛋白相关的蛋白质，参与DMD的发病机制，因为在DMD和mdx后肢肌肉中发现小窝数量增加。小窝因其所含的血管内皮生长因子（VEGF）受体而影响血管生成。mdx小鼠的口面部肌肉会发生肌肉坏死，随后进行肌肉再生。为了确定小窝蛋白和VEGF在营养不良性咀嚼肌发病机制中的作用，我们检测了对照小鼠和mdx小鼠中小窝蛋白-1（cav-1）、小窝蛋白-3（cav-3）和VEGF的表达。在mdx咀嚼肌中，未发现VEGF转录水平和蛋白水平有变化，而cav-1和cav-3的表达增加。通过免疫组织化学发现，再生肌纤维中小窝蛋白-3有强烈的肌膜染色。此外，用小窝蛋白-1抗体进行免疫组织化学显示，在有再生肌纤维的区域血管数量增加。营养不良性咀嚼肌在cav-1和cav-3的表达上显示出与后肢肌肉类似的变化。mdx小鼠颌肌中的血管生成似乎未受影响。我们推测小窝蛋白表达增加可能导致广泛而有效的肌肉再生。
