一种含有转化生长因子β调控元件的硫代磷酸酯寡脱氧核苷酸作为一种新型局部非甾体类抗纤维化药物发挥作用。
A sense phosphorothioate oligodeoxynucleotide containing the transforming growth factor beta regulatory element acts as a novel local nonsteroidal antifibrotic drug.
作者信息
Cutroneo K R, Chiu J F
机构信息
Department of Biochemistry, College of Medicine, University of Vermont Burlington, Vermont 05405, USA.
出版信息
Wound Repair Regen. 2000 Sep-Oct;8(5):399-404. doi: 10.1111/j.1524-475x.2000.00399.x.
Fibrosis is a potential response to tissue injury. At present, glucocorticoids with their numerous toxic side effects are the only effective treatment for fibrotic diseases. Granulomas induced by sponge implantation were treated with single-stranded phosphorothioate oligodeoxynucleotides containing the wild type or mutated transforming growth factor-beta response element designed to inhibit the rat proalpha1(I) promoter activity. Single-stranded phosphorothioate oligonucleotides resulted in antifibrotic activity based on their ability to reduce granuloma tissue formation and selectively inhibit collagen synthesis. The mutated single-standed phosphorothioate oligonucleotides or dexamethasone given at an equivalent dose to single-standed phosphorothioate oligonucleotides failed to do so. These data suggest that the phosphorothioate oligodeoxynucleotide containing the transforming growth factor-beta regulatory element has an antifibrotic effect and may be used to inhibit the development of fibrosis.
纤维化是对组织损伤的一种潜在反应。目前，具有众多毒副作用的糖皮质激素是治疗纤维化疾病的唯一有效方法。用含有野生型或突变型转化生长因子-β反应元件的单链硫代磷酸酯寡脱氧核苷酸处理海绵植入诱导的肉芽肿，这些反应元件旨在抑制大鼠原α1（I）启动子活性。单链硫代磷酸酯寡核苷酸基于其减少肉芽肿组织形成和选择性抑制胶原蛋白合成的能力而产生抗纤维化活性。给予与单链硫代磷酸酯寡核苷酸等效剂量的突变单链硫代磷酸酯寡核苷酸或地塞米松则无法做到这一点。这些数据表明，含有转化生长因子-β调控元件的硫代磷酸酯寡脱氧核苷酸具有抗纤维化作用，可用于抑制纤维化的发展。
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