Skeletal muscle regeneration in facioscapulohumeral muscular dystrophy is correlated with pathological severity.
Skeletal muscle regeneration in facioscapulohumeral muscular dystrophy is correlated with pathological severity.
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DOI：
10.1093/hmg/ddaa164
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发表时间：
2020-09-29
影响因子：
3.5
通讯作者：
Zammit PS
中科院分区：
文献类型：
--
作者：
Banerji CRS;Henderson D;Tawil RN;Zammit PS
面肩肱型肌营养不良症（FSHD）是一种以缓慢进行性骨骼肌无力和消瘦为特征的常染色体显性肌病。虽然在许多肌营养不良症中经常引起再生反应，但对FSHD肌肉中是否定期引起再生反应知之甚少，促使这项研究。为了比较，我们还检查了类似的缓慢进展的强直性肌营养不良2型（DM 2）。为了首先在转录组水平上研究再生，我们使用了200个人类基因Hallmark Myogenesis列表。与成肌细胞对应物相比，该肌生成生物标志物在FSHD和对照健康肌管中升高，因此在肌生成分化中更高。与对照活检相比，来自大多数独立的FSHD、DM 2或杜氏肌营养不良（DMD）研究的肌肉活检和每种疾病的荟萃分析中，肌生成生物标志物也升高。此外，肌生成生物标志物是来自对照的FSHD、DM 2和DMD的稳健的二元分类。我们还分析了肌肉再生的蛋白质水平的免疫标记肌肉活检的发展肌球蛋白重链。这种免疫标记显示，在76%的FSHD肌肉活检中，四头肌有一个或多个再生肌纤维，胫骨前肌有91%。股四头肌活检的平均再生肌纤维比例为0.48%，显著低于胫骨前肌的1.72%。所有DM 2肌肉活检均含有再生肌纤维，每次活检平均为1.24%。FSHD中的肌肉再生与纤维尺寸变化、中央成核、纤维化和坏死/再生/炎症的病理标志相关。总之，FSHD肌肉活检中的再生反应与病理学的严重程度相关。
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant myopathy characterized by slowly progressive skeletal muscle weakness and wasting. While a regenerative response is often provoked in many muscular dystrophies, little is known about whether a regenerative response is regularly elicited in FSHD muscle, prompting this study. For comparison, we also examined the similarly slowly progressing myotonic dystrophy type 2 (DM2). To first investigate regeneration at the transcriptomic level, we used the 200 human gene Hallmark Myogenesis list. This myogenesis biomarker was elevated in FSHD and control healthy myotubes compared to their myoblast counterparts, so is higher in myogenic differentiation. The myogenesis biomarker was also elevated in muscle biopsies from most independent FSHD, DM2 or Duchenne muscular dystrophy (DMD) studies compared to control biopsies, and on meta-analysis for each condition. In addition, the myogenesis biomarker was a robust binary discriminator of FSHD, DM2 and DMD from controls. We also analysed muscle regeneration at the protein level by immunolabelling muscle biopsies for developmental myosin heavy chain. Such immunolabelling revealed one or more regenerating myofibres in 76% of FSHD muscle biopsies from quadriceps and 91% from tibialis anterior. The mean proportion of regenerating myofibres per quadriceps biopsy was 0.48%, significantly less than 1.72% in the tibialis anterior. All DM2 muscle biopsies contained regenerating myofibres, with a mean of 1.24% per biopsy. Muscle regeneration in FSHD was correlated with the pathological hallmarks of fibre size variation, central nucleation, fibrosis and necrosis/regeneration/inflammation. In summary, the regenerative response in FSHD muscle biopsies correlates with the severity of pathology.
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影响因子：
16.6
作者：
Banerji CRS;Panamarova M;Hebaishi H;White RB;Relaix F;Severini S;Zammit PS
通讯作者：
Zammit PS
影响因子：
1.2
作者：
Boldrin, Luisa;Zammit, Peter S.;Morgan, Jennifer E.
通讯作者：
Morgan, Jennifer E.
影响因子：
2.8
作者：
Decary, S;Ben Hamida, C;Butler-Browne, GS
通讯作者：
Butler-Browne, GS
影响因子：
3.6
作者：
GROUNDS, MD;GARRETT, KL;BEILHARZ, MW
通讯作者：
BEILHARZ, MW
影响因子：
3.5
作者：
Gabriëls, J;Beckers, MC;Belayew, A
通讯作者：
Belayew, A