PITX2 增强了病态骨骼肌干细胞的再生潜能。
PITX2 Enhances the Regenerative Potential of Dystrophic Skeletal Muscle Stem Cells.
机构信息
Cardiac and Skeletal Myogenesis Group, Department of Experimental Biology, University of Jaén, CU Las Lagunillas B3-362, Jaén 23071, Spain.
Servicio de Neurología, Hospital Universitario Virgen de las Nieves, Granada 18014, Spain.
出版信息
Stem Cell Reports. 2018 Apr 10;10(4):1398-1411. doi: 10.1016/j.stemcr.2018.03.009.
Duchenne muscular dystrophy (DMD), one of the most lethal genetic disorders, involves progressive muscle degeneration resulting from the absence of DYSTROPHIN. Lack of DYSTROPHIN expression in DMD has critical consequences in muscle satellite stem cells including a reduced capacity to generate myogenic precursors. Here, we demonstrate that the c-isoform of PITX2 transcription factor modifies the myogenic potential of dystrophic-deficient satellite cells. We further show that PITX2c enhances the regenerative capability of mouse DYSTROPHIN-deficient satellite cells by increasing cell proliferation and the number of myogenic committed cells, but importantly also increasing dystrophin-positive (revertant) myofibers by regulating miR-31. These PITX2-mediated effects finally lead to improved muscle function in dystrophic (DMD/mdx) mice. Our studies reveal a critical role for PITX2 in skeletal muscle repair and may help to develop therapeutic strategies for muscular disorders.
杜氏肌营养不良症（DMD）是一种最致命的遗传性疾病，其特征是肌肉逐渐退化，导致肌肉萎缩。DMD 患者的肌萎缩蛋白缺失会对肌肉卫星干细胞产生严重影响，包括产生成肌前体细胞的能力下降。在这里，我们证明了 PITX2 转录因子的 c 异构体改变了营养不良性卫星细胞的成肌潜能。我们进一步表明，PITX2c 通过增加细胞增殖和肌生成细胞的数量来增强小鼠 DYSTROPHIN 缺乏的卫星细胞的再生能力，但重要的是，它还通过调节 miR-31 增加肌营养不良蛋白阳性（回复）肌纤维的数量。这些 PITX2 介导的作用最终导致 DMD（mdx）小鼠的肌肉功能得到改善。我们的研究揭示了 PITX2 在骨骼肌修复中的关键作用，并可能有助于为肌肉疾病开发治疗策略。
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