Dexamethasone induces dysferlin in myoblasts and enhances their myogenic differentiation
Dexamethasone induces dysferlin in myoblasts and enhances their myogenic differentiation
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DOI：
10.1016/j.nmd.2009.12.003
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发表时间：
2010-02-01
影响因子：
2.8
通讯作者：
Jamieson, Christina A. M.
中科院分区：
文献类型：
--
作者：
Belanto, Joseph J.;Diaz-Perez, Silvia V.;Jamieson, Christina A. M.
糖皮质激素在许多肌营养不良症中是有益的，但它们在治疗dysferlin病中是无效的，dysferlin病是一种由dysferlin丢失引起的罕见的肌营养不良症。我们试图通过研究糖皮质激素对成肌细胞系C2C12和dysferlin缺陷型C2C12细胞分化的影响来理解这种差异的分子基础。我们发现，药理剂量的地塞米松增强了C2C12的肌源性融合效率，并增加了dysferlin的诱导，沿着特异性肌源性转录因子、肌膜和结构蛋白。相反，dysferlin缺陷的C2C12细胞系表现出减少长肌管和早期诱导特定的肌肉分化蛋白，最值得注意的是，肌球蛋白重链。地塞米松部分逆转了dysferlin缺陷C2C12细胞中肌源性融合的缺陷。我们假设糖皮质激素的一个关键治疗益处可能是dysferlin作为糖皮质激素增强肌源性分化的重要组分的上调。(C)2009 Elsevier B.V.保留所有权利。
Glucocorticoids are beneficial in many muscular dystrophies but they are ineffective in treating dysferlinopathy, a rare muscular dystrophy caused by loss of dysferlin. We sought to understand the molecular basis for this disparity by studying the effects Of a glucocorticoid on differentiation of the myoblast cell line, C2C12, and dysferlin-deficient C2C12s. We found that pharmacologic doses of dexamethasone enhanced the myogenic fusion efficiency of C2C12s and increased the induction of dysferlin, along with specific myogenic transcription factors, sarcolemmal and structural proteins. In contrast, the dysferlin-deficient C2C12 cell line demonstrated a reduction in long myotubes and early induction of particular muscle differentiation proteins, most notably, myosin heavy chain. Dexamethasone partially reversed the defect in myogenic fusion in the dysferlin-deficient C2C12 cells. We hypothesize that a key therapeutic benefit Of glucocorticoids may be the up-regulation of dysferlin as an important component of glucocorticoid-enhanced myogenic differentiation. (C) 2009 Elsevier B.V. All rights reserved.