Voluntary wheel running improves molecular and functional deficits in a murine model of facioscapulohumeral muscular dystrophy.
Voluntary wheel running improves molecular and functional deficits in a murine model of facioscapulohumeral muscular dystrophy.
复制标题
自愿跑轮改善面肩肱型肌营养不良小鼠模型的分子和功能缺陷。
DOI：
10.1016/j.isci.2023.108632
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发表时间：
2024-01-19
期刊：
影响因子：
5.8
通讯作者：
Chen, Yi-Wen
中科院分区：
文献类型：
--
作者：
Bittel, Adam J.;Bittel, Daniel C.;Gordish-Dressman, Heather;Chen, Yi-Wen
耐力运动训练对骨骼肌健康有益，但目前尚不清楚这种类型的运动是否可以靶向或纠正面肩肱型肌营养不良症（FSHD）的分子机制。使用FLExDUX 4小鼠FSHD模型，其特征在于慢性，低水平的病理性双同源异型盒蛋白4（DUX 4）基因表达，我们表明，6周的自愿，自由轮跑步改善了跑步性能，力量，线粒体功能和肌膜修复能力，同时减缓/逆转骨骼肌纤维化。这些改善与调节肌动蛋白细胞骨架信号传导、血管重塑、炎症、纤维化和肌肉质量的基因网络/途径的转录活性恢复到野生型（WT）水平相关。然而，FLExDUX 4小鼠在训练和缺氧、炎症、血管生成和细胞骨架途径的持续转录过度激活的情况下表现出线粒体含量的钝化增加。这些结果确定了FSHD中运动反应性和非反应性分子通路，同时为使用间歇性运动作为非侵入性治疗选择提供了支持。与野生型（WT）小鼠相比，FLExDUX 4小鼠更虚弱，每天跑的距离更短FLExDUX 4小鼠与WT小鼠相比具有肌膜修复缺陷和纤维化升高自愿轮跑（VWR）将FLexDUX 4基因表达恢复至WT水平VWR改善FLexDUX 4膜修复、强度、线粒体功能和纤维化生物科学;病理生理学;转录组学
Endurance exercise training is beneficial for skeletal muscle health, but it is unclear if this type of exercise can target or correct the molecular mechanisms of facioscapulohumeral muscular dystrophy (FSHD). Using the FLExDUX4 murine model of FSHD characterized by chronic, low levels of pathological double homeobox protein 4 (DUX4) gene expression, we show that 6 weeks of voluntary, free wheel running improves running performance, strength, mitochondrial function, and sarcolemmal repair capacity, while slowing/reversing skeletal muscle fibrosis. These improvements are associated with restored transcriptional activity of gene networks/pathways regulating actin cytoskeletal signaling, vascular remodeling, inflammation, fibrosis, and muscle mass toward wild-type (WT) levels. However, FLExDUX4 mice exhibit blunted increases in mitochondrial content with training and persistent transcriptional overactivation of hypoxia, inflammatory, angiogenic, and cytoskeletal pathways. These results identify exercise-responsive and non-responsive molecular pathways in FSHD, while providing support for the use of endurance-type exercise as a non-invasive treatment option. FLExDUX4 mice are weaker and run shorter distances per day vs. wild-type (WT) mice FLExDUX4 mice have sarcolemmal repair deficits and elevated fibrosis vs. WT mice Voluntary wheel running (VWR) restores FLExDUX4 gene expression toward WT levels VWR improves FLExDUX4 membrane repair, strength, mitochondrial function, and fibrosis Biological sciences; Pathophysiology; Transcriptomics
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影响因子：
4
作者：
Liu R;Krüger K;Pilat C;Fan W;Xiao Y;Seimetz M;Ringseis R;Baumgart-Vogt E;Eder K;Weissmann N;Mooren FC
通讯作者：
Mooren FC
影响因子：
5
作者：
Pettersson S;Edin F;Hjelte C;Scheinost D;Wagner S;Ekblom B;Jessen N;Madsen K;Andersson-Hall U
通讯作者：
Andersson-Hall U
影响因子：
6
作者：
Paleo, Brian J.;McElhanon, Kevin E.;Bulgart, Hannah R.;Banford, Kassidy K.;Beck, Eric X.;Sattler, Kristina M.;Goines, Briana N.;Ratcliff, Shelby L.;Crowe, Kelly E.;Weisleder, Noah
通讯作者：
Weisleder, Noah
DOI：
10.3390/diagnostics12030561
发表时间：
2022-02-22
期刊：
Diagnostics (Basel, Switzerland)
影响因子：
--
作者：
Laghi V;Ricci V;De Santa F;Torcinaro A
通讯作者：
Torcinaro A
影响因子：
1.6
作者：
Bankole, Landry-Cyrille;Millet, Guillaume Y.;Feasson, Leonard
通讯作者：
Feasson, Leonard