Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells.
Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells.
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微阵列分析表明，乳腺上皮细胞中的halofuginone激活了综合应力反应。
DOI：
10.1186/1756-0500-4-381
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发表时间：
2011-10-05
影响因子：
1.8
通讯作者：
Whitman M
中科院分区：
文献类型：
--
作者：
Kamberov YG;Kim J;Mazitschek R;Kuo WP;Whitman M
小分子Halofuginone（HF）是细胞外基质（ECM）基因表达的有效调节剂，具有独特的治疗潜力。虽然HF作用的基础尚不清楚，但TGFβ信号传导的抑制和氨基酸限制性反应（AAR）的激活已分别与许多ECM组分的HF转录控制以及通过调节Th17细胞分化改善纤维化和减轻自身免疫性疾病有关。本研究的目的是在上皮细胞中产生HF靶点的全局表达谱，以鉴定该细胞类型中HF功能的潜在介质。我们报道了HF对上皮细胞中ECM重塑蛋白Mmp13表达的调节与先前报道的HF对TGFβ信号抑制的影响是分开的，并使用微阵列表达分析将其与综合应激反应（ISR）的转录反应特征相关联。我们的研究结果表明，ISR的激活可能是HF生物学效应的共同机制。
The small molecule Halofuginone (HF) is a potent regulator of extracellular matrix (ECM ) gene expression and is unique in its therapeutic potential. While the basis for HF effects is unknown, inhibition of TGFβ signaling and activation of the amino acid restriction response (AAR) have been linked to HF transcriptional control of a number of ECM components and amelioration of fibrosis and alleviation of autoimmune disease by regulation of Th17 cell differentiation, respectively. The aim of this study was to generate a global expression profile of HF targets in epithelial cells to identify potential mediators of HF function in this cell type. We report that HF modulation of the expression of the ECM remodeling protein Mmp13 in epithelial cells is separable from previously reported effects of HF on TGFβ signal inhibition, and use microarray expression analysis to correlate this with transcriptional responses characteristic of the Integrated Stress Response (ISR). Our findings suggest activation of the ISR may be a common mechanism underlying HF biological effects.