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General Pharmacology
Pines, M., Institute of Animal Science, Agric. Res. Org., Volcani C., Bet Dagan, Israel
Nagler, A., Dept. of Bone Marrow Transplantation, Hadassah University Hospital, 91120, Jerusalem, Israel
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 α1(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 α1(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 α1(I) synthesis specifically and transiently at the transcriptional level suggests that this material fulfills the criteria for a successful and effective anti-fibrotic therapy.
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Halofuginone: A novel antifibrotic therapy
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Pines, M., Institute of Animal Science, Agric. Res. Org., Volcani C., Bet Dagan, Israel
Nagler, A., Dept. of Bone Marrow Transplantation, Hadassah University Hospital, 91120, Jerusalem, Israel
Halofuginone: A novel antifibrotic therapy
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 α1(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 α1(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 α1(I) synthesis specifically and transiently at the transcriptional level suggests that this material fulfills the criteria for a successful and effective anti-fibrotic therapy.
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