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不同肌肉中 d-肌聚糖缺失型肌营养不良症小鼠模型的组织学特征和肌球蛋白蛋白水平的差异。

Differential histological features and myogenic protein levels in distinct muscles of d-sarcoglycan null muscular dystrophy mouse model.

机构信息

Catedrático CONACYT, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico.

Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico.

出版信息

J Mol Histol. 2023 Aug;54(4):405-413. doi: 10.1007/s10735-023-10136-7. Epub 2023 Jun 26.

Abstract

Skeletal muscle (SkM) comprises slow and fast-twitch fibers, which differ in molecular composition, function, and systemic energy consumption. In addition, muscular dystrophies (DM), a group of diverse hereditary diseases, present different patterns of muscle involvement, progression, and severity, suggesting that the regeneration-degeneration process may differ depending on the muscle type. Therefore, the study aimed to explore the expression of proteins involved in the repair process in different muscles at an early stage of muscular dystrophy in the δ-sarcoglycan null mice (Sgcd-null), a limb-girdle muscular dystrophy 2 F model. Hematoxylin & Eosin (H&E) Staining showed a high number of central nuclei in soleus (Sol), tibialis (Ta), gastrocnemius (Gas), and extensor digitorum longus (Edl) from four months Sgcd-null mice. However, fibrosis, determined by trichrome of Gomori modified staining, was only observed in Sgcd-null Sol. In addition, the number of Type I and II fibers variated differentially in the Sgcd-null muscles vs. wild-type muscles. Besides, the protein expression level of β-catenin, myomaker, MyoD, and myogenin also presented different expression levels in all the Sgcd-null muscles studied. In summary, our study reveals that muscles with different metabolic characteristics showed distinct expression patterns of proteins involved in the muscle regeneration process. These results could be relevant in designing therapies for genetic and acquired myopathy.

摘要

骨骼肌(SkM)由慢肌和快肌纤维组成,它们在分子组成、功能和全身能量消耗方面存在差异。此外,肌肉营养不良症(DM)是一组不同的遗传性疾病,其肌肉受累、进展和严重程度呈现不同的模式,这表明再生-退化过程可能因肌肉类型而异。因此,本研究旨在探索不同肌肉中参与修复过程的蛋白质在δ-肌聚糖缺失小鼠(Sgcd-null)的肌肉营养不良早期阶段的表达,Sgcd-null 是一种肢带型 2F 肌肉营养不良模型。苏木精和伊红(H&E)染色显示,四个月大的 Sgcd-null 小鼠的比目鱼肌(Sol)、胫骨前肌(Ta)、腓肠肌(Gas)和趾长伸肌(Edl)中存在大量中央核。然而,只有在 Sgcd-null Sol 中观察到改良 Gomori 三色染色法确定的纤维化。此外,Sgcd-null 肌肉与野生型肌肉的 I 型和 II 型纤维数量存在差异。此外,β-连环蛋白、肌生成素、MyoD 和肌细胞生成素的蛋白表达水平在所有研究的 Sgcd-null 肌肉中也呈现出不同的表达水平。总之,我们的研究表明,具有不同代谢特征的肌肉表现出不同的肌肉再生过程中参与蛋白的表达模式。这些结果对于设计针对遗传和获得性肌病的治疗方法可能具有重要意义。

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