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FHL1 regulates myoblast differentiation and autophagy through its interaction with LC3

机译:FHL1调节成肌细胞分化自噬通过其与LC3的交互

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摘要

Four and a half LIM domain protein 1 (FHL1) belongs to the FHL protein family and is predominantly expressed in skeletal and cardiac muscle. FHL1 acts as a scaffold during sarcomere assembly and plays a vital role in muscle growth and development. Autophagy is key to skeletal muscle development and regeneration, with its dysfunction associated with a range of muscular pathologies and disorders. In this study, we constructed FHL1-silenced or FHL1-overexpressed myoblasts to investigate its role in autophagy during the differentiation of chicken myoblasts into myotubules. Our data showed that FHL1 contributes to myoblast differentiation as measured through MyoG, MyoD, Myh3, and Mb mRNA expression, MyoG and MyHC protein expression and the morphological characteristics of myoblasts. The results showed that FHL1 silencing inhibited the expression of ATG5 and ATG7, meanwhile, immunofluorescence and immunoprecipitation showed that FHL1 and LC3 interacted to regulate the correct formation of autophagosomes. FHL1 inhibition increased cleaved caspase-3 and PARP abundance and promoted myoblast apoptosis. Furthermore, FHL1 rescued skeletal muscle atrophy through regulating the expression of Atrogin-1 and MuRF1. Taken together, these data suggested that FHL1 regulates chicken myoblast differentiation through its interaction with LC3.
机译:四个半LIM域蛋白1 (FHL1)属于飞毛腿蛋白质和家人主要表现在骨骼和心脏肌肉。装配,在肌肉的生长起着至关重要的作用和发展。肌肉发育和再生的功能障碍相关的一系列肌肉病理和疾病。构建FHL1-silenced或FHL1-overexpressed成肌细胞来研究其在自噬作用在鸡成肌细胞的分化myotubules。对成肌细胞分化测量通过MyoG MyoD, Myh3, Mb mRNA表情,MyoG MyHC蛋白质表达和成肌细胞的形态特征。结果表明,FHL1沉默抑制与此同时,ATG5的表达和ATG7免疫荧光和免疫沉淀反应FHL1 LC3调节互动正确的自噬小体的形成。抑制增加裂解caspase-3和PARP丰富和促进成肌细胞凋亡。此外,FHL1获救骨骼肌萎缩通过调节Atrogin-1的表达和MuRF1。FHL1调节鸡成肌细胞通过其与LC3分化。

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