Halofuginone: A novel antifibrotic therapy

被引:126
作者
Pines, M [1 ]
Nagler, A
机构
[1] Agr Res Org, Volcani Ctr, Inst Anim Sci, IL-50250 Bet Dagan, Israel
[2] Hadassah Univ Hosp, Dept Bone Marrow Transplantat, IL-91120 Jerusalem, Israel
来源
GENERAL PHARMACOLOGY | 1998年 / 30卷 / 04期
关键词
collagen; cirrhosis; fibrosis; scleroderma; graft versus host disease;
D O I
10.1016/S0306-3623(97)00307-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. Fibrosis is characterized by extracellular matrix deposition, of which collagen type I is the major constituent. The progressive accumulation of connective tissue resulted in destruction of normal tissue architecture and function. 2. Fibrosis is a common response to various insults or injuries and can be the outcome of any perturbation in the cellular function of any tissue. 3. Halofuginone was found to inhibit collagen alpha 1(I) gene expression and collagen synthesis in a variety of cell cultures including human fibroblasts derived from patients with excessive skin collagen type I synthesis. 4. Halofuginone was found to inhibit collagen alpha 1(I) gene expression and collagen synthesis in animal models characterized by excessive deposition of collagen. In these models, fibrosis was induced in various tissues such as skin, liver, lung, etc. Halofuginone was injected intraperitoneally, added to the foodstuff or applied locally. 5. Halofuginone decreased skin collagen in a chronic graft-versus-host disease patient. 6. The ability of extremely low concentrations of halofuginone to inhibit collagen alpha 1(I) synthesis specifically and transiently at the transcriptional level suggests that this material fulfills the criteria for a successful and effective anti-fibrotic therapy. (C) 1998 Elsevier Science Inc.
引用
收藏
页码:445 / 450
页数:6
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