Minetti G C, Colussi C, Adami R, Serra C, Mozzetta C, Parente V, Fortuni S, Straino S, Sampaolesi M, Di Padova M, Illi B, Gallinari P, Steinkühler C, Capogrossi M C, Sartorelli V, Bottinelli R, Gaetano C, Puri P L
Dulbecco Telethon Institute at Fondazione A. Cesalpino, Institute of Cell Biology and Tissue Engineering, San Raffaele Biomedical Science Park of Rome, Via Castel Romano 100, 00128, Rome, Italy.
Nat Med. 2006 Oct;12(10):1147-50. doi: 10.1038/nm1479. Epub 2006 Sep 17.
Pharmacological interventions that increase myofiber size counter the functional decline of dystrophic muscles. We show that deacetylase inhibitors increase the size of myofibers in dystrophin-deficient (MDX) and alpha-sarcoglycan (alpha-SG)-deficient mice by inducing the expression of the myostatin antagonist follistatin in satellite cells. Deacetylase inhibitor treatment conferred on dystrophic muscles resistance to contraction-coupled degeneration and alleviated both morphological and functional consequences of the primary genetic defect. These results provide a rationale for using deacetylase inhibitors in the pharmacological therapy of muscular dystrophies.
增加肌纤维大小的药理学干预可对抗营养不良性肌肉的功能衰退。我们发现，去乙酰化酶抑制剂可通过诱导卫星细胞中肌肉生长抑制素拮抗剂卵泡抑素的表达，增加肌营养不良蛋白缺陷（MDX）小鼠和α-肌聚糖（α-SG）缺陷小鼠的肌纤维大小。去乙酰化酶抑制剂治疗赋予营养不良性肌肉对收缩偶联性退变的抵抗力，并减轻了原发性基因缺陷的形态学和功能后果。这些结果为在肌肉营养不良症的药物治疗中使用去乙酰化酶抑制剂提供了理论依据。
