Effect of halofuginone on the development of tight skin (TSK) syndrome
Effect of halofuginone on the development of tight skin (TSK) syndrome
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DOI：
10.1080/0891693021000001235
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发表时间：
2002-07-01
期刊：
影响因子：
3.5
通讯作者：
Bona, C
中科院分区：
文献类型：
--
作者：
McGaha, T;Kodera, T;Bona, C
硬皮病致病事件的终点是皮肤和内脏器官的纤维化。硬皮病中的纤维化是由结缔组织中胶原蛋白的过度合成和沉积引起的。硬皮病的发病率和死亡率非常高，目前尚无特效治疗方法。 Halofuginone 是一种在治疗硬皮病方面具有巨大潜力的药物，因为它抑制成纤维细胞合成 I 型胶原蛋白。我们研究了卤常酮对紧皮（TSK）小鼠的体内作用，这些小鼠由于遗传缺陷而自发患上硬皮病样疾病。我们的结果表明，当给新生小鼠施用卤常酮时，可以防止皮肤硬化的发生；当对成年 TSK 小鼠施用时，卤常酮可以减少皮肤增生。这些效应与合成胶原基因转录本的细胞数量减少以及人类靶抗原特异性自身抗体水平降低相关。这些结果表明，halofuginome 可用作治疗纤维化疾病的治疗剂。
The end point of pathogenic events in scleroderma is fibrosis of the skin and internal organs. Fibrosis in scleroderma results from the over synthesis and deposition of collagen in the connective tissue. The morbidity and mortality of the scleroderm is very high and presently there is no specific treatment. Halofuginone is a drug with great potential for the treatment of scleroderma since it inhibits the synthesis of collagen type I by fibroblasts. We have studied the in vivo effect of halofuginone in tight skin (TSK) mice that spontaneously develop a scleroderma-like disease due to a genetic defect. Our results demonstrate that halofuginone prevented the occurrence of skin sclerosis when administered to newborn mice and reduced cutaneous hyperplasia when administered in adult TSK mice. These effects correlated with a decreased number of cells synthesizing collagen gene transcripts and a reduction in the level of autoantibodies specific for human target antigens. These results indicate that halofuginome may have use as a therapeutic in the treatment of fibrotic disease.