Involvement of ERK signaling in halofuginone-driven inhibition of fibroblast ability to contract collagen lattices

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• 作者：Charlotte Tacheau ; Laurence Michel ; Dominique Farge ; Alain Mauviel ; Franck Verrecchia
• 关键词：Halofuginone ; Fibrosis ; Extracellular matrix contraction ; Tissue repair
• 刊名：European Journal of Pharmacology
• 出版年：2007
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：14 November 2007
• 卷：573
• 期：1-3
• 页码：65-69
• 文件大小：456 K

摘要

Halofuginone, an alkaloid isolated from the plant Dichroa febrifuga, has been shown to be a potent inhibitor of tissue fibrosis. We herein demonstrate that, at concentrations below 10^{− 7} M, halofuginone does not affect the cell cycle but efficiently induces extracellular signal-regulated kinases_1,2 (ERK_1,2), p38 and Jun NH2-terminal kinases_1,2 (JNK_1,2) phosphorylation. In addition, at these non cytotoxic concentrations, halofuginone diminishes the capacity of fibroblasts to contract mechanically unloaded collagen lattices, an effect that is specifically blocked by the ERK inhibitors PD98059 and U0126, not by inhibitors of the JNK or p38 pathways. These data thus indicate that the inhibitory effect of halofuginone on fibroblast contractile activity, a key function for wound healing implicated in the development of tissue fibrosis, is an ERK-mediated mechanism.