Differential gene expression in the rat skeletal and heart muscle in glucocorticoid-induced myopathy: Analysis by microarray
Differential gene expression in the rat skeletal and heart muscle in glucocorticoid-induced myopathy: Analysis by microarray
复制标题
DOI：
10.1023/a:1027352703783
复制
发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
Miyata, T
中科院分区：
文献类型：
--
作者：
Komamura, K;Shirotani-Ikejima, H;Miyata, T
糖皮质激素的使用会导致高血压、心肌肥厚和全身肌病。本研究分析了地塞米松(0.5 mg/100g，连续3d)或地塞米松联合胰岛素样生长因子-1(0.35 mg/100g，连续3d)对大鼠腓肠肌和左室心肌差异基因表达的影响。地塞米松引起腓肠肌萎缩。组织蛋白酶L，而不是泛素，是地塞米松诱导骨骼肌蛋白分解的最早的介导物。胰岛素样生长因子-1逆转了腓肠肌质量，并删除了地塞米松下调的部分基因。另一方面，地塞米松的应用不会导致心肌肥厚或高血压。地塞米松在心肌中仅上调前列腺素D合成酶基因，下调与细胞外基质和蛋白水解酶抑制相关基因的表达。肥大的分子改变可能已经开始。地塞米松诱导的蛋白分解和胰岛素样生长因子-1逆转在骨骼肌中迅速发生，但在心肌中相对延迟。
Administration of glucocorticoids results in hypertension, cardiac hypertrophy, and general myopathy. The present study analyzed the acute effect of dexamethasone (0.5 mg/100 g for 3 days) or dexamethasone plus insulin-like growth factor-1 (0.35 mg/100 g for 3 days) on differential gene expression in the gastrocnemius muscle and the left ventricular myocardium of rats. Dexamethasone induced atrophy of gastrocnemius muscle. Cathepsin L, and not ubiquitin, was the earliest mediator of skeletal muscle proteolysis induced by dexamethasone. Insulin-like growth factor-1 reversed gastrocnemius muscle mass, and deleted a part of downregulated genes by dexamethasone. On the other hand, dexamethasone administration did not result in cardiac hypertrophy or hypertension. Only prostaglandin D synthase gene was upregulated by dexamethasone in myocardium, and genes related to extracellular matrix and proteinase inhibitor were downregulated. Molecular alteration for hypertrophy might have initiated. Dexamethasone-induced proteolysis and reversal with insulin-like growth factor-1 occurred rapidly in skeletal muscle; but was relatively delayed in the myocardium.