Güttsches Anne-K, Balakrishnan-Renuka Ajeesh, Kley Rudolf André, Tegenthoff Martin, Brand-Saberi Beate, Vorgerd Matthias
Department of Neurology, Heimer-Institute at the BG University-Hospital Bergmannsheil GmbH, Ruhr University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany,
Histochem Cell Biol. 2015 May;143(5):443-52. doi: 10.1007/s00418-014-1299-6. Epub 2014 Dec 17.
Regenerating muscle fibers emerge from quiescent satellite cells, which differentiate into mature multinuclear myofibers upon activation. It has recently been found that ATOH8, a bHLH transcription factor, is regulated during myogenic differentiation. In this study, expression and localization of ATOH8, the other well-described regeneration markers, vimentin, nestin and neonatal myosin, and the satellite cell marker Pax7 were analyzed on protein level in human myopathy samples by immunofluorescence studies. On mRNA level, expression levels of ATOH8 and vimentin were studied by quantitative real-time PCR. ATOH8 is expressed in activated satellite cells and proliferating myoblasts of human skeletal muscle tissue. Quantitative analyses of ATOH8+, Pax7+, vimentin+, nestin+ and neonatal myosin+ muscle fibers showed the highest amount of regenerating muscle fibers in inflammatory myopathies, followed by muscular dystrophy. The relative co-expression of ATOH8 with the above-mentioned markers did not vary among the disorders. These results show that the novel regeneration marker ATOH8 contributes to muscle cell differentiation in healthy and diseased human muscle tissue.
再生肌纤维源自静止的卫星细胞,这些卫星细胞在激活后会分化为成熟的多核肌纤维。最近发现,一种bHLH转录因子ATOH8在肌源性分化过程中受到调控。在本研究中,通过免疫荧光研究在蛋白质水平上分析了人类肌病样本中ATOH8、其他已充分描述的再生标志物波形蛋白、巢蛋白和新生儿肌球蛋白以及卫星细胞标志物Pax7的表达和定位。在mRNA水平上,通过定量实时PCR研究了ATOH8和波形蛋白的表达水平。ATOH8在人类骨骼肌组织的激活卫星细胞和增殖成肌细胞中表达。对ATOH8+、Pax7+、波形蛋白+、巢蛋白+和新生儿肌球蛋白+肌纤维的定量分析表明,炎症性肌病中再生肌纤维数量最多,其次是肌肉营养不良。ATOH8与上述标志物的相对共表达在不同疾病之间没有差异。这些结果表明,新型再生标志物ATOH8在健康和患病的人类肌肉组织中对肌肉细胞分化有贡献。